Biology Reference
In-Depth Information
The relationship of DdM7 to another FERM myosin, M10
A number of unconventional myosins possess the combined MyTH4/FERM
module in their tail regions (Berg et al., 2001). These include the class VII, X,
XII and XV myosins. Inspection of phylogenetic trees of the myosin
superfamily reveals that the class VII and X myosins are related to each
other (Hodge and Cope, 2000; Berg et al., 2001). Of interest is the fact that
DdM7 comes off quite early after the class VII and X myosins diverge. Unlike
mammalian M7, myosin X (M10) is expressed more widely as might be
expected for a myosin with a shared function in higher and lower eukaryotes
(Berg et al., 2000). The M10 tail domain shares some features with that of the
M7 tail. It has a stretch of predicted coiled-coil followed by three
phospholipid binding PH domains and then a MyTH4/FERM module
(Berg et al., 2000) (Figure 2.1). While the presence of the three PH domains is
unique to M10 it is worth noting that the FERM domain contains a PH fold
(Pearson et al., 2000), suggesting that there may be some shared or related
function between these two modules. The PH domains of M10 have been
shown to bind to the products of phosphatidylinositol 3-kinase (PI3K)
(Isakoff et al., 1998) and the FERM domain of ERM proteins has been shown
to bind to PI(4,5)P
2
(Niggli et al., 1995; Hirao et al., 1996). Ongoing
investigations into the membrane and potential phospholipid association of
M7 and M10 may clarify the significance of the structural homology between
the PH and FERM domains.
Further underscoring the potential shared functions of DdM7 and M10, the
distribution of M10 is remarkably similar to that of DdM7. It is also found in
dynamic, actin rich regions of the cell as well as in filopodia (Berg et al., 2000;
Berg and Cheney, 2002). M10 also appears to play a role in filopod formation
as overexpression results in the production of increased numbers of filopodia
(Berg and Cheney, 2002). In contrast to DdM7, M10 appears to participate in
the movement of particles up and down the shaft of the filopodium and it has
been proposed that motor-driven movement powers the transport of materials
out to the tip of the filopod and the motor then is passively moved out of the
filopodium via actin flow (Berg and Cheney, 2002). M10 is expressed in
macrophages where it is localized to the phagocytic cup (Cox et al., 2002).
Treatment of these cells with the PI3K inhibitor wortmannin results in loss of
this localization. Overexpression of the M10 tail region encompassing the
three PH domains along with the MyTH4/FERM domain significantly
inhibits phagocytosis in a size-dependent manner, with the internalization of
6 mm beads being inhibited while that of 2 mm beads is not. Microinjection of
antibodies directed against the motor domain of M10 into macrophages also
inhibits phagocytosis. The inhibitory effect of M10 tail expression does not
appear to be due to a lack of adhesion but rather to a reduction in the ability
of the cells to spread along a surface (Cox et al., 2002) suggesting differences
