Talin

Talin

Page updated 10/6/02

Provides a link between actin microfilaments and the plasma membrane. Talin is a fairly large protein (actual mol.wt 270 kDa, but appears to be 235 kDa on gels), which gave it the original name of p235 (Collier & Wang 1982a,b). When the first sequence became available (Rees et al, 1990) it was clear that talin belonged to the band 4.1 family, and was composed of an N-terminal globular domain and a . Talin nucleates actin assembly and binds to vinculins in addition to a host of actin binding proteins and other proteins mainly at the focal adhesion (Table 1) (a). As well as binding to vinculin which itself associated with lipids it has been reported that talin also is able to bind lipids directly (Goldmann et al, 1992; Dietrich et al, 1993).

Talin-binding protein	Function	Reference
actin	component of microfilaments	Kaufmann et al, 1991; Schmidt et al, 1999
pp125^FAK	A tyrosine protein kinase	Chen et al, 1995; Borowsky & Hynes, 1998
layilin	A trans-membranous glycoprotein	Borowsky & Hynes, 1998
vinculin	pivotal component of the focal contact	Burridge & Mangeat, 1984; Bass et al, 2002
b-integrin	Trans-membranous adhesion protein	Horwitz et al, 1986; Burn et al,1988; Knezevic et al, 1996; Calderwood et al, 2002
Myosin II	Contractile protein	Lin et al, 1998
Dystrophin	Giant protein absent in Duchenne Muscular Dystrophy .	Senter et al, 1993
Table 1 Talin binding partners

The structure of Talin.
Talin has been shown to be a head-to tail dimeric protein that adopts a "dumbbell" shape by E.M. (Goldmann et al, 1994). The protein is easily digested (thrombin, calpain II) into two domains 47kDa and a 200kDa (Niggli et al, 1994). The 47kDa fragment later determined to be the N-terminus (Rees et al, 1990) binds anionic lipids (Niggli et al, 1994), whereas the high helical content C-terminal tail forms a number of repeats (McLachlan et al, 1994).

The actin -binding sites of talin and the affects of the protein on actin polymerization and structure.
Talin is presently thought to contain three different actin binding sites (Hemmings et al, 1996), through these talin has a complex relationship with actin. On the one hand the early work concluded that talin reduced filament length (Collier & Wang, 1982a; Goldmann et al, 1994) and reduced the viscosity of actin solutions (Collier & Wang, 1982a), on the other talin has been found to nucleate actin assembly (Kaufmann et al, 1992). The interaction between actin and talin is very pH sensitive (Schmidt et al, 1993; Goldmann et al, 1999).

The interaction of talin with vinculin
Talin and vinculin are two pivotal components of the focal adhesion. The introduction of antibodies against talin to cells disrupts focal adhesion and the phosphorylation of vinculin by also disrupts focal adhesions (). The two proteins have been shown to interact (Burridge & Mangeat, 1984), and there are three distinct vinculin binding sites on talin (Hemmings et al, 1996)

Other variant Talin molecules
In addition to the talin homolog TALA, Dictyostelium also has another talin-like molecule (TALB) that has a C-terminal extension that is homologous to the villin headpiece domain (found in a number of other actin binding proteins) (Tsujioka et al, 1999).

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