Open Access

Integrin triplets of marine sponges in the murine and human MHCI-CD8 interface and in the interface of human neural receptor heteromers and subunits

SpringerPlus20132:128

DOI: 10.1186/2193-1801-2-128

Received: 23 October 2012

Accepted: 11 March 2013

Published: 22 March 2013

Abstract

Based on our theory, main triplets of amino acid residues have been discovered in cell-adhesion receptors (integrins) of marine sponges, which participate as homologies in the interface between two major immune molecules, MHC class I (MHCI) and CD8αβ. They appear as homologies also in several human neural receptor heteromers and subunits. The obtained results probably mean that neural and immune receptors also utilize these structural integrin triplets to form heteromers and ion channels, which are required for a tuned and integrated intracellular and intercellular communication and a communication between cells and the extracellular matrix with an origin in sponges, the oldest multicellular animals.

Keywords

Neural receptor-receptor interactions Receptor interface Marine sponges Triplet homologies

Introduction

Based on a mathematical approach, Tarakanov and Fuxe (2010 , 2011) have deduced a set of triplet homologies (so called ‘triplet puzzle’) that may be responsible for protein-protein interactions, including receptor heteromers and human immunodeficiency virus (HIV) entry. For example, the triplet of amino acid residues ITL (Ile-Thr-Leu) appears in both receptors of any of six receptor heteromers: GABAB1-GABAB2 (GABAB receptor), GABAB1-mGluR1, GABAB1-CXCR4, CXCR4-CCR2, 5HT1B-5HT1D, and MHC class I MHCI-CD8. At the same time, this triplet ITL does not appear in both receptors of any of known non-heteromers (GABAB2-A2A, A2A-D1, A1-D2, NTSR1-D1, TSHR-D2, and CD4-D2; see Tarakanov and Fuxe 2010). According to recent biochemical studies (Borroto-Escuela et al. 2010 , 2011, 2012a b; Romero-Fernandez et al. 2011), such triplets exist in the interacting domains forming the receptor interface. Furthermore, a ‘guide-and-clasp’ manner of receptor-receptor interactions has been proposed where the ‘adhesive guides’ may be the triplet homologies (Tarakanov and Fuxe, 2010). According to recent bioinformatic studies (Tarakanov et al. 2012 a b c d), several triplet homologies of such receptor heteromers in human brain may be the same as in cell-adhesion receptors of marine sponges, known to be highly conserved from the lowest metazoa to vertebrates (Gamulin et al. 1994; Muller 1997; Pancer et al. 1997; Buljan and Bateman 2009). Interactions between such triplets probably represent a general molecular mechanism for receptor-receptor interactions (Fuxe et al 2012) and may play an important role in human learning (Agnati et al. 2003) and some diseases (Tarakanov et al. 2009).

In the current paper, many of such triplets have been found in integrins of marine sponges together with human alpha and beta integrins. This means that such triplet homologies may play a role in alpha-beta heterodimeric complexes forming integrin receptors and interact with extracellular matrix proteins (Barczyk et al. 2010). Of especial interest is that the same integrin triplets exist also in the murine and human MHCI interface with CD8, in human neural receptors and in the interface of both protomers of several receptor heteromers. The presence of such triplet homologies in several receptor subunits building up the neuromuscular nicotinic cholinergic receptors has also been demonstrated. At least one of the homologies may have a role in the intermolecular subunit interactions of this ion channel receptor.

Methods

Amino acid codes of receptors and other proteins have been obtained from the National Center for Biotechnology Information (http://​www.​ncbi.​nlm.​nih.​gov) and the Universal Protein Resource (http://​www.​uniprot.​org). Table 1 summarizes data on proteins used. In abstract mathematical terms, any protein is just a word coded by a 20-letter alphabet where triplet is any 3-letter subword. Thus, triplet homology is any triplet which exists in both given words. Our theory of triplet puzzle supposes some basic set of triplets as a code that determines whether two receptors bind or not (Tarakanov and Fuxe 2010). None of the widely used software like Clustal (http://​www.​clustal.​org/​), AGGRESCAN (http://​bioinf.​uab.​es/​aggrescan/​), accelrys (http://​accelrys.​com/​), and so on seems to be able to deal with so specific and complicated combinatorial puzzle. Our original software has been developed to determine such basic set of triplet homologies from two given sets of protein-protein pairs (which bind and do not bind). The core of this software is the computing of all triplet homologies between two given words (but not only their alignment like in the above mentioned Clustal). The method consists in forming the binary matrix of all one-letter homologies (which element is 1 if there is homology and 0 otherwise) and then filtering this matrix using rather specific rules of so called cellular automata (for example, see Tarakanov and Prokaev 2007; http://​youtu.​be/​1DevThU5fyM).
Table 1

Data on proteins used

Protein

Species

Type

Accession code

ITGA

Sponge (Geodia cydonium)

Metazoan adhesion receptor subunit Integrin-α

CAA65943

ITGB

Sponge (Geodia cydonium)

Metazoan adhesion receptor subunit Integrin-β

CAA77071

ITGB4

Sponge (Marichromatium purpuratum)

Metazoan adhesion receptor subunit Integrin-β4

ZP_08774040

MHCI

Mouse (Mus musculus)

H-2 class I histocompatibility antigen

NP_001001892

CD8a

Mouse

T-cell surface glycoprotein chain CD8α

NP_001074579

CD8b

Mouse

T-cell surface glycoprotein chain CD8β

NP_033988

MHCI

Human (Homo sapiens)

H-2 class I histocompatibility antigen

AAA59599

CD8a

Human

T-cell surface glycoprotein chain CD8α

NP_001139345

CD8b

Human

T-cell surface glycoprotein chain CD8β

NP_757362)

CXCR4

Human

Chemokine receptor

P61073

TSHR

Human

Thyroid stimulating hormone receptor

NP_000360

FGFR1

Human

Fibroblast growth factor receptor

NP_075598

5HT1A

Human

Serotonin receptor

AAH69159

Collagen

Human

Matrix protein

P02452

ITGAIIB

Human

Integrin receptor subunit-αIIb

P08514

ITGAL

Human

Integrin receptor subunit-αL

P20701

ITGAM

Human

Integrin receptor subunit-αM

NP_001139280

ITGAV

Human

Integrin receptor subunit-αV

EAX10934

ITGAX

Human

Integrin receptor subunit-αX

NP_000878

ITGB2

Human

Integrin receptor subunit-β2

NP_000202

ITGB3

Human

Integrin receptor subunit-β3

NP_000203

ITGB4

Human

Integrin receptor subunit-β4

NP_000204

ITGB5

Human

Integrin receptor subunit-β5

NP_000205

ITGB6

Human

Integrin receptor subunit-β6

P18564

ITGB8

Human

Integrin receptor subunit-β8

P26012

ACHA

Human

Acetylcholine receptor subunit-α

P02708

ACHB

Human

Acetylcholine receptor subunit-β

P11230

ACHD

Human

Acetylcholine receptor subunit-δ

Q07001

ACHE

Human

Acetylcholine receptor subunit-ε

Q04844

mGluR1

Human

Metabotropic glutamate receptor

NP_000829

GABAB2

Human

γ-aminobutyric acid receptor subunit-2

O75899

GABAB1

Human (Homo sapiens)

γ-aminobutyric acid receptor subunit-1

NP_001461

GABAB1

Mouse (Mus musculus)

"

NP_062312

GABAB1

Norway rat (Rattus norvegicus)

"

NP_112290

GABAB1

Western clawed frog (Xenopus (Silurana) tropicalis)

"

NP_001107291

GABAB1

Green puffer (Tetraodon nigroviridis)

"

uniprot/Q4S9D9

GABAB1

Zebrafish (Danio rerio)

"

NP_001070794

GABAB1

African malaria mosquito (Anopheles gambiae)

"

uniprot/Q7PME5

GABAB1

Drosophila pseudoobscura

"

XP_001357356

GABAB1

Human body louse (Pediculus humanus corporis)

"

XP_002430445

GABAB1

Caenorhabditis elegans

"

ACE63490

Table 2

Example of integrin triplets of marine sponges in murine and human proteins

Protein

Species

Type

LLG

GLL

ITL

RPA

GDR

RDG

DGR

ITGA

Sponge

Integrin-α

-

-

+

+

+

-

-

ITGB

Sponge

Integrin-β

+

+

-

-

-

-

-

ITGB4

Sponge

Integrin-β

-

-

-

-

-

+

+

MHC Class I

Mouse

Immune receptor

+

-

+

+

-

-

+

CD8a

Mouse

Immune receptor

+

-

+

-

-

-

-

CD8b

Mouse

Immune receptor

-

-

-

-

-

-

-

MHC Class I

Human

Immune receptor

+

-

+

+

-

+

+

CD8a

Human

Immune receptor

-

-

+

+

-

-

-

CD8b

Human

Immune receptor

-

+

+

-

-

-

-

CXCR4

Human

Immune receptor

-

-

+

-

-

-

-

TSHR

Human

Endocrine receptor

-

-

-

+

-

-

-

FGFR1

Human

Receptor tyrosine kinase

-

-

-

+

-

-

-

5HT1A

Human

Neural receptor

+

-

-

-

-

-

-

Collagen

Human

Matrix protein

-

-

-

-

+

+

+

ITGAIIB

Human

Integrin-α

+

+

-

-

-

+

+

ITGAL

Human

Integrin-α

-

+

-

-

-

-

-

ITGAM

Human

Integrin-α

+

+

-

-

-

-

-

ITGAV

Human

Integrin-α

+

+

-

-

-

-

-

ITGAX

Human

Integrin-α

+

+

+

-

+

 

-

ITGB2

Human

Integrin-β

-

+

-

-

-

-

+

ITGB3

Human

Integrin-β

-

+

-

-

-

-

+

ITGB4

Human

Integrin-β

+

-

-

-

-

-

-

ITGB5

Human

Integrin-β

+

-

-

-

-

+

-

ITGB6

Human

Integrin-β

-

+

-

-

-

-

-

ITGB8

Human

Integrin-β

-

+

-

-

+

-

-

ACHA

Human

Neural receptor subunit

+

-

-

-

-

-

-

ACHB

Human

Neural receptor subunit

+

-

+

+

+

-

-

ACHD

Human

Neural receptor subunit

-

+

+

+

-

-

-

ACHE

Human

Neural receptor subunit

+

+

-

-

-

-

-

GABAB1

Human

Neural receptor

+

+

+

-

-

-

-

GABAB2

Human

Neural receptor

-

+

+

-

-

-

-

mGluR1

Human

Neural receptor

-

+

+

-

-

-

-

(+ yes, - no).

Table 3

Example of integrin triplets of marine sponges in the protomers of human receptor heteromers and in subunits of the neuromuscular nicotinic receptor

Receptor heteromer

Reference

Function

LLG

GLL

ITL

RPA

DGR

MHCI-CD8a

Gao et al. (1997)

Adaptive immune response

-

-

#

+

-

Wang et al. (2009)

MHC1-CD8b

Wang et al. (2009)

Adaptive immune response

-

-

#

-

-

CD8a-CD8b

Wang et al. (2009)

Coreceptor of T cells

-

-

+

-

-

ITGAIIB-ITGB3

Barczyk et al. (2010)

RGD (Arg-Gly-Asp) receptor

-

#

-

-

#

ITGAV-ITGB3

Barczyk et al. (2010)

RGD receptor

-

#

-

-

-

ITGAV-ITGB5

Barczyk et al. (2010)

RGD receptor

#

-

-

-

-

ITGAV-ITGB6

Barczyk et al. (2010)

RGD receptor

-

#

-

-

-

ITGAV-ITGB8

Barczyk et al. (2010)

RGD receptor

-

#

-

-

-

ITGAL-ITGB2

Barczyk et al. (2010)

Leukocyte receptor

-

+

-

-

-

ITGAM-ITGB2

Barczyk et al. (2010)

Leukocyte receptor

-

+

-

-

-

ITGAX-ITGB2

Barczyk et al. (2010)

Leukocyte receptor

-

+

-

-

-

GABAB1-GABAB2

Marshall et al. (2001)

Activation of the potassium channels and regulation of receptor trafficking

-

#

#

-

-

GABAB1-mGluR1

Hirono et al. (2001)

Modulation of excitatory transmission

-

#

+

-

-

GABAB1-CXCR4

Guyon and Nahon (2007)

Modulation of neuroendocrine systems

-

-

#

-

-

ACHA-ACHB

Changeux et al. 1984

Part of the neuromuscular nicotinic receptor

+

-

-

-

-

ACHA-ACHE

Changeux et al. 1984

Part of the neuromuscular nicotinic receptor

+

-

-

-

-

ACHB-ACHD

Changeux et al. 1984

Part of the neuromuscular nicotinic receptor

-

-

+

#

-

(+ yes in both receptors, # may mediate their interaction, - no in any receptor).

No experimental research has been performed on humans and/or animals.

Results

The triplets ITL (Ile-Thr-Leu), RPA (Arg-Pro-Ala), DGR (Asp-Gly-Arg), LLG (Leu-Leu-Gly), and GLL (Gly-Leu-Leu) of the integrin receptors of marine sponges appear as homologies in murine and human MHCI, GABAB1, and human integrin receptor heteromers (see Tables 2 and 3, Figures 1 and 2). The triplets ITL (Ile-Thr-Leu) and DGR (Asp-Gly-Arg) are particularly interesting. For example, the triplet ITL is in the interface providing the binding between MHCI and CD8αβ (Wang et al. 2009). This triplet homology exists also in three GABAB1 receptor heteromers of human brain: GABAB1-GABAB2 forming the GABAB receptor (Marshall et al. 2001), GABAB1-mGluR1, and GABAB1-CXCR4 and may mediate the interaction in two of them (see Table 3 and Figure 1). In the first two heteromers also triplet GLL (Gly-Leu-Leu) may participate in the interaction (see Table 3 and Figure 2).
https://static-content.springer.com/image/art%3A10.1186%2F2193-1801-2-128/MediaObjects/40064_2012_Article_182_Fig1_HTML.jpg
Figure 1

Example of the triplets ITL, RPA, and DGR (dark-shaded letters) in the integrins of marine sponges existing in the murine (underlined) and human MHCI-CD8 complex, human collagen (DGR triplet), and human receptor heteromers: TM1, TM2 and TM7 are the first, the second and the seventh transmembrane α-helices of ACHB, CXCR4, and GABAB (GABAB1-GABAB2 heteromer) receptors, respectively, and contain the ITL triplet. The RPA triplet is also found in the TSHR and FGFR1; the RPA but not the ITL triplet homologies are in a position to contribute to the physical interaction between the beta and delta subunits of the neuromuscular nicotinic receptor (ACHB-ACHD); light-shaded letters are positively charged amino acids (R, K, and H), whereas dark-shaded white letters are negatively charged amino acids (D and E); bold letters are main players of leucine-rich motifs (L, S, and C).

https://static-content.springer.com/image/art%3A10.1186%2F2193-1801-2-128/MediaObjects/40064_2012_Article_182_Fig2_HTML.jpg
Figure 2

Example of the triplets LLG and GLL (dark-shaded letters) in the integrins of marine sponges, murine (underlined) and human MHC Class I and human receptor heteromers.

The triplet DGR (Asp-Gly-Arg) is in fact the inverse triplet of RGD (Arg-Gly-Asp) that provides the binding site for integrin RGD-binding receptors (see Table 3). Moreover, a small peptide ligand RGD (Arg-Gly-Asp) that mimics extracellular matrix protein binding to integrins also causes impairments in plasticity at glutamatergic synapses (Wiggins et al. 2011).

The evolution of the ITL triplet in the GABAB1 receptor subunit is displayed in Figure 3. In phylogeny, it appears to begin in fish (Tetraodon) and then continues to man, while it is missing in zebrafish (Danio rerio). Thus, the usefulness of the ITL triplet in recognition is rediscovered in the fish GABAB1 receptor.
https://static-content.springer.com/image/art%3A10.1186%2F2193-1801-2-128/MediaObjects/40064_2012_Article_182_Fig3_HTML.jpg
Figure 3

The triplet ITL (dark-shaded letters) during the evolution of GABAB1 subunit: CAEEL (Caenorhabditis elegans), LOUSE(Pediculus humanus corporis), DROPS(Drosophila pseudoobscura), ANOGA(Anopheles gambiae), DANRE(Danio rerio), TETNG(Tetraodon nigroviridis), FROG(Xenopus tropicalis), RAT(Rattus norvegicus), MOUSE(Mus musculus), and HUNAN(Homo sapiens); asterisk (*) marks homologies (F and L); quote (') marks leucine-like homologies (L and I); bold letters are main players of leucine-rich motifs (L, S, and C).

Furthermore, the RPA triplet homology in the beta and delta interacting nicotinic subunits of the neuromuscular nicotinic receptor (see Changeux et al. 1984) is in a location (N-terminal parts of ACHB and ACHD) where it may participate in forming part of their interface (see Figure 1 and Table 3).

Discussion

The triplet ITL (Ile-Thr-Leu) found in integrins of marine sponges is presented as a homology in the interface between MHC Class I and CD8αβ heterodimer (coreceptor in T cells). It is postulated that this triplet homology can contribute to the formation of the MHCI-CD8 heteromeric complex which leads to a strong activation of the T cell by guiding the T-cell receptor into relevant self-MHC recognition (see Wang et al. 2009). Thus, it seems possible that the ITL triplet may have a critical role in the interaction between these two immune receptors which is necessary for appropriate T cell function. A mutation of the ITL triplet in these immune receptors will be of value to test this hypothesis. The indications have also been obtained that triplet homology ITL in the N-terminal of beta and delta nicotinic receptor subunits of the neuromuscular nicotinic receptor may help mediate their interaction in the subunit interface.

Conclusion

Integrin triplets of marine sponges found in the interface of human receptor heteromers and even in the interface between two major immune molecules MHCI-CD8 seem to confirm once more our theory. This triplet puzzle arose as a surprising merger of pure mathematics and most recent biochemical studies of receptor-receptor interactions. As a result, it appears that neural and immune receptor heteromers in humans may also utilize these structural elements originating in sponges, the oldest multicellular animals. Thus, the triplet puzzle may be an ancient and general mechanism for protein-protein recognition.

Declarations

Acknowledgement

The authors have not received any support for this work.

Authors’ Affiliations

(1)
Russian Academy of Sciences, St. Petersburg Institute for Informatics and Automation
(2)
Department of Neuroscience, Karolinska Institutet

References

  1. Agnati LF, Franzen O, Ferre S, Leo G, Franco R, Fuxe K: Possible role of intramembrane receptor-receptor interactions in memory and learning via formation of long-lived heteromeric complexes: focus on motor learning in the basal ganglia. J Neural Transm Suppl 2003, 65: 1-28. 10.1007/978-3-7091-0643-3_1View Article
  2. Barczyk M, Carracedo S, Gullbeerg D: Integrins. Cell Tissue Res 2010, 339: 269-280. 10.1007/s00441-009-0834-6View Article
  3. Borroto-Escuela DO, Narvaez M, Marcellino D, Parrado C, Narvaez JA, Tarakanov AO, Agnati LF, Diaz-Cabiale Z, Fuxe K: Galanin receptor-1 modulates 5-hydroxtryptamine-1A signaling via heterodimerization. Bioch Biophys Res Commun 2010, 393: 767-772. 10.1016/j.bbrc.2010.02.078View Article
  4. Borroto-Escuela DO, Tarakanov AO, Guidolin D, Ciruela F, Agnati LF, Fuxe K: Moonlight characteristics of G protein-coupled receptors: focus on receptor heteromers and relevance for neurodegeneration. IUBMB Life 2011, 63: 463-472. 10.1002/iub.473View Article
  5. Borroto-Escuela DO, Romero-Fernandez W, Mudo G, Perez-Alea M, Ciruela F, Tarakanov AO, Narvaez M, Di Liberto V, Agnati LF, Belluardo N, Fuxe K: FGFR1-5-HT1A heteroreceptor complexes and their enhacement of hippocampal plasticity. Biol Psych 2012a, 71: 84-91. 10.1016/j.biopsych.2011.09.012View Article
  6. Borroto-Escuela DO, Romero-Fernandez W, Perez-Alea M, Narvaez M, Tarakanov AO, Mudo G, Agnati LF, Ciruela F, Belluardo N, Fuxe K: The existence of FGFR1-5-HT1A receptor heterocomplexes in midbrain 5-HT neurons of the rat: relevance for neuroplasticity. J Neurosci 2012b, 32: 6295-6303. 10.1523/JNEUROSCI.4203-11.2012View Article
  7. Buljan M, Bateman A: The evolution of protein domain families. Biochem Soc Trans 2009, 37: 751-755. 10.1042/BST0370751View Article
  8. Changeux JP, Devillers-Thiéry A, Chemouilli P: Acetylcholine receptor: an allosteric protein. Science 1984, 225: 1335-1345. 10.1126/science.6382611View Article
  9. Fuxe K, Borroto-Escuela DO, Marcellino D, Romero-Fernandez W, Frankowska M, Guidolin D, Filip M, Ferraro L, Woods AS, Tarakanov A, Ciruela F, Agnati LF, Tanganelli S: GPCR heteromers and their allosteric receptor-receptor interactions. Curr Med Chem 2012, 19: 356-363. 10.2174/092986712803414259View Article
  10. Gamulin V, Rinkevich B, Schäcke H, Kruse M, Müller IM, Müller WE: Cell adhesion receptors and nuclear receptors are highly conserved from the lowest metazoa (marine sponges) to vertebrates. Biol Chem Hoppe Seyler 1994, 375: 583-588.View Article
  11. Gao GF, Tormo J, Gerth UC, Wyer JR, McMichael AJ, Stuart DI, Jakobsen NK: Crystal structure of the complex between human CD8α and HLA-A2. Nature 1997, 387: 630-634. 10.1038/42523View Article
  12. Guyon A, Nahon JL: Multiple actions of the chemokine stromal cell-derived factor 1a on neuronal activity. J Mol Endocrinol 2007, 38: 365-376. 10.1677/JME-06-0013View Article
  13. Hirono M, Yoshioka T, Konishi S: GABA(B) receptor activation enhances mGluR-mediated responses at cerebellar excitatory synapses. Nat Neurosci 2001, 4: 1207-1216.View Article
  14. Marshall FH, Jones KA, Kaupmann K, Bettler B: GABAB receptors – the first 7TM heterodimers. Trends Pharmacol Sci 2001, 20: 396-399.View Article
  15. Muller WEG: Origin of metazoan adhesion molecules and adhesion receptors as deduced from cDNA analyses in the marine sponge Geodia cydonium : a review. Cell Tissue Res 1997, 289: 383-395. 10.1007/s004410050885View Article
  16. Pancer Z, Kruse M, Muller I, Muller WEG: On the origin of metazoan adhesion receptors: Cloning of integrin α subunit from the sponge Geodia cydonium . Mol Biol Evol 1997, 14: 391-398. 10.1093/oxfordjournals.molbev.a025775View Article
  17. Romero-Fernandez W, Borroto-Escuela DO, Tarakanov AO, Mudo G, Narvaez M, Perez-Alea M, Agnati LF, Ciruela F, Belluardo N, Fuxe K: Agonist-induced formation of FGFR1 homodimers and signaling differ among members of the FGF family. Biochem Biophys Res Commun 2011, 409: 764-768. 10.1016/j.bbrc.2011.05.085View Article
  18. Tarakanov AO, Fuxe KG: Triplet puzzle: homologies of receptor heteromers. J Mol Neurosci 2010, 41: 294-303. 10.1007/s12031-009-9313-5View Article
  19. Tarakanov AO, Fuxe KG: The triplet puzzle of homologies in receptor heteromers exists also in other types of protein-protein interactions. J Mol Neurosci 2011, 44: 173-177. 10.1007/s12031-011-9511-9View Article
  20. Tarakanov A, Prokaev A: Identification of cellular automata by immunocomputing. J Cellular Automata 2007, 2: 39-45.
  21. Tarakanov AO, Fuxe KG, Agnati LF, Goncharova LB: Possible role of receptor heteromers in multiple sclerosis. J Neural Transm 2009, 116: 989-994. 10.1007/s00702-009-0197-xView Article
  22. Tarakanov AO, Fuxe KG, Borroto-Escuela DO: On the origin of the triplet puzzle of homologies in receptor heteromers: Immunoglobulin triplets in different types of receptors. J Mol Neurosci 2012a, 46: 616-621. 10.1007/s12031-011-9649-5View Article
  23. Tarakanov AO, Fuxe KG, Borroto-Escuela DO: On the origin of the triplet puzzle of homologies in receptor heteromers: toll-like receptor triplets in different types of receptors. J Neural Transm 2012b, 119: 517-523. 10.1007/s00702-011-0734-2View Article
  24. Tarakanov AO, Fuxe KG, Borroto-Escuela DO: Integrin triplets of marine sponges in human brain receptor heteromers. J Mol Neurosci 2012c, 48: 154-160. 10.1007/s12031-012-9793-6View Article
  25. Tarakanov AO, Fuxe KG, Borroto-Escuela DO: Integrin triplets of marine sponges in human D2 receptor heteromers. J Recept Sig Transd 2012d, 32: 202-208. 10.3109/10799893.2012.692119View Article
  26. Wang R, Natarajan K, Margulies DH: Structural basis of the CD8ab/MHCI interaction: focused recognition orients CD8b to a T cell proximal position. J Immunol 2009, 183: 2554-2564. 10.4049/jimmunol.0901276View Article
  27. Wiggins A, Smith RJ, Shen HW, Kalivas PW: Integrins modulate relapse to cocain-seeking. J Neurosci 2011, 31: 16177-16184. 10.1523/JNEUROSCI.3816-11.2011View Article

Copyright

© Tarakanov and Fuxe; licensee Springer. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.