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Figure 2.1 Schematic illustration of the FERM proteins M7, M10 and talin. Shown are
box diagrams of each molecule, with the individual domains indicated. The motor domain
of Dictyostelium M7 (DdM7) is shaded grey, the light chain-binding IQ motifs are dark
ovals, the region of predicted coiled-coil is indicated by C, the MyTH4 domains by M,
FERM domains by the stippled box and the SH3 domain by the lighter grey box. The
heavy chain of M10 has a PEST sequence in the N-terminal region of the tail and the region
spanning the 3 PH domains is indicated by the dark box (3X PH). TalinA (TalA) and
TalinB (TalB) are also shown, each with their N-terminal FERM domains and C-terminal
actin-biding regions (AB). TalB also possess a villin headpiece (VH) at its C-terminus
Simson et al., 1998). Interestingly, Ca 2+ -dependent cell-cell binding of
aggregating cells is reduced significantly in the talA null mutant (Niewo¨ hner et
al., 1997).
Talins also play a role in multicellular development. Dictyostelium cells
lacking TalB stream and form mounds normally but halt at this stage as they
fail to form a tip that is associated with differentiation (Tsujioka et al., 1999).
However, cells in the talB null mounds do undergo cell differentiation
properly suggesting that the block in development is due to a failure in
morphogenesis. These results indicate that the two talins have unique roles
in Dictyostelium and continued analysis of TalB should reveal its role in
adhesion in development. Deletion of talin from mouse embryonic stem cells
results in the inability of undifferentiated cells to adhere to laminin and lower
levels of b1 integrin. Homozygous talin null mice are not viable and die at 8.5
to 9.5 days post-coitum, due to defects in cell migration at gastrulation
(Monkley et al., 2000). These results show that the role of talin has been
generally conserved throughout evolution.
M7 is an actin-based motor protein essential for hearing in humans, mice
and zebrafish and adhesion in Dictyostelium (Gibson et al., 1995; Weil et al.,
1995; Titus, 1999; Ernest et al., 2000; Tuxworth et al., 2001). The M7a heavy
chain comprises an N-terminal motor domain and a tail region that has a brief
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