Selective tetraspan–integrin complexes (CD81/α4β1, CD151/α3β1, CD151/α6β1) under conditions disrupting tetraspan interactions

Abstract

The tetraspans are molecules with four transmembrane domains which are engaged in multimolecular complexes (the tetraspan web) containing a subset of beta1 integrins (in particular alpha3beta1, alpha4beta1 and alpha6beta1), MHC antigens and several unidentified molecules. The molecules associated with tetraspans are readily detected after immunoprecipitation performed in mild detergents such as Brij 97 or CHAPS. In this study we show that another classical mild detergent, digitonin, dissociated most of these associated molecules, including integrins, from the tetraspans CD9, CD37, CD53, CD63, CD82, Co-029, Talla-1 and NAG-2. In contrast, reciprocal immunoprecipitations from various cell lines demonstrated that two other tetraspans, CD81 and CD151, formed complexes with integrins not disrupted by digitonin. These complexes were CD81/alpha4beta1, CD151/alpha3beta1 and CD151/alpha6beta1. Furthermore, a new anti-CD151 monoclonal antibody (mAb), TS151r, was shown to have a restricted pattern of expression, inversely related to the sum of the levels of expression of alpha6beta1 and alpha3beta1. This mAb was unable to co-precipitate integrins in digitonin, suggesting that its epitope is blocked by the association with integrins. Indeed, the binding of TS151r to the cell surface was quantitatively diminished following alpha3beta1 overexpression. Altogether, these data suggest that, among tetraspans, CD81 interacts directly with the integrin alpha4beta1, and CD151 interacts directly with integrins alpha3beta1 and alpha6beta1. Because all tetraspan-tetraspan associations are disrupted by digitonin, it is likely that the other tetraspans interact indirectly with integrins, through interactions with CD81 or CD151.

Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151

“…20,21 Other integrins (a5b1, a6b1, a6b4 and aIIbb3) are also known to interact with CD151 depending on cell types, [22][23][24][25] although information about the binding sites is not available. Since CD151 is located at the periphery of the thin invasive protrusions (invadopodia) of cancer cells and treatment of the cells with anti-CD151 monoclonal antibody inhibits metastasis, 26 this molecule is considered to play an important role in invasion and metastasis.…”

Les tétraspanines dans la physiopathologie de la peau

“…Dans la décennie qui suivit, la fonction dans la régu-lation de ces processus cellulaires d'autres tétraspa-nines, en interaction avec les intégrines, a été étudiée. Ainsi, par des expériences d'immunofluorescence, il a été montré que les protéines CD9, CD81 et CD151 sont fortement exprimées dans les kératinocytes en culture α3β1, α6β1 et α4β1 [5][6][7] pour réguler leurs fonctions, comme l'attestent des expériences de mutagenèse dirigée visant à introduire des mutations dans les domaines fonctionnels de CD151 [8][9][10]. Les tétraspanines possèdent une structure commune comprenant quatre régions hydrophobes hautement conservées, transmembranaires, flanquées de courtes séquences intracytoplasmiques N-et C-terminales et de deux boucles extracellulaires de tailles inégales (les domaines EC1 et EC2) (Figure 1).…”

Age-Related Changes in Cochlear Gene Expression In Normal and Shaker 2 Mice

“…These were Tm4sf3, Aim1, Dbi, and Gas6. TM4SF3, a small tetraspan membrane protein, interacts with other tetraspanins as well as a subset of b1 integrins (a3b1, a4b1, a6b1) (Serru et al 1999). Aim1 (absent in melanoma 1) encodes a nonlens member of the bg-crystallin superfamily (Ray et al 1997;Rajini et al 2003) that may interact with the cytoskeleton, based on AIM1's homology to a member of the gelsolin superfamily of actin-binding proteins (Teichmann et al 1998).…”