Myosin IX

Myosin IX
Updated 21/5/'02
Myosin IX (Myr5, Myr7) members have been discovered in vertebrates and the nematode Caenorhabditis elegans (Berg et al, 2001). Myosin IX (Inoue et al, 2002) and myosin VI are the only myosin motors to be minus end directed! Myosin IX is widely expressed in many cell types (Reinard et al, 1995; Wirth et al, 1996) especially compared to myosin VI, and so it is supposed that most minus end directed motility in cells is due to myosin IX (see Minus end Myosins). Myosin IX is generally cytoplasmic but partly associated with vesicles, the plasma-membrane and microfilaments (Chieregatti et al, 1989;). There are 2 myosin IX genes in mice (Hasson et al, 1996). Human myosin IXA is suspected to be the cause of a form of Bardet-Biedl syndrome, an autosomal recessive disorder featuring obesity, short stature, retinitis pigmentosa and mental retardation (Gorman et al, 1999).
	The structure of myosin IX is similar to myosin III in that they both have N-terminal extensions, but these are different. The extension of myosin III is a kinase, whereas that of myosin IX is of unknown function and has no presently recognised homology. The tail region has a zinc binding motif and a Rho/Rac GTPase activating domain. The main feature of note is that myosin IX is monomeric.
The human myosin IXb gene is expressed as two differentially spliced forms one with a proline-rich C-terminus and the other with a longer unique C-terminus (Post et al, 1998). Human myosin IXb is a GAP (GTPase activating protein) for the G-protein Rho (Chieregatti et al, 1989; Post et al,1998; Reinhard et al, 1995), meaning that it is likely to be involved in the activation of the Rho pathway itself a known activator of myosin II mediated contraction. It has been suggested that processivity (how long a motor molecule remains attached to the cytoskeleton producing continuous motility) of motor protein is a function of having two heads (to increase the likelihood that the motor remains attached), and in the case on myosins, that the head remains bound even in the presence of ATP Myosin IXb is reported to be highly processive (Post et al, 2002; Inoue et al, 2002), and cosediments with actin even in the presence of ATP (Post et al, 1989), yet there is good evidence to suggest that myosin IXb is a single headed motor (Post et al, 2002). A mutant lacking the tail domain was shown to be monomeric and still support processive motility of actin filaments (Inoue et al, 2002). These authors suggested that like the analogous situation with the single headed kinesis KIF1A, myosin IX may have a second, actin binding domain that tethers the motor to the microfilament between power strokes. The similarity between myosins III and IX has lead to the suggestion that both are motorized signalling molecules (Bähler, 2000).
References:- Bähler, M. (2000) Are class III and class IX myosins motorized signalling molecules? BBA. 1496, 52-59. Berg, J. S., Powell, B. C. & Cheney, R. E. (2001) A millennial myosin census. Mol.Biol.Cell. 12, 780-794. Chieregatti, E., Gärtner, A., Stöffler, H.-E. & Bähler, M. (1998) Myr 7 is a novel myosin IX-RhoGap expressed in rat brain. J.Cell Sci. 111, 3597-3608. Gorman, S. W., Haider, N. B., Grieshammer, U., Swiderski, R. E., Kim, E., Welch, J. W., Searby, C., Leng, S., Carmi, R., Sheffield, V. C. & Duhl, D. M. (1999) The cloning and developmental expression of unconventional myosin IXA (MYO9A) a gene in the Bardet-Biedl syndrome (BBS4) region at chromosome 15q22-q23. Genomics. 59, 150-160. Hasson, T., Skowron, J. F., Gilbert, D. J., Avraham, K. B., Perry, W. L., Bement, W. M., Anderson, B. L., Sherr, E. H., Chen, Z. Y., Greene, L. A., Ward, D. C., Corey, D. P., Mooseker, M. S., Copeland, N. G. & Jenkins, N. A. (1996) Mapping of unconventional myosins in mouse and human. Genomics. 36, 431-439. Inoue, A., Saito, J., Ikebe, R. & Ikebe, M. (2002) Myosin IXb is a single-headed minus-end-directed processive motor. Nature Cell Biol. 4, 302-306. Post, P. L., Bockoch, G. M. & Mooseker, M. S. (1998) Human myosin-IX is a mechanochemically active motor and a GAP for Rho., J.Cell Sci. 111, 941-950. Post, P. L., Tyska, M. J., O'Connell, C. B., Johung, K., Hayward, A. & Mooseker, M. S. (2002) Myosin-IXb is a single-headed and processive motor. J.Biol.Chem. 277, 11679-11683. Reinhard, J., Scheel, A. A., Diekmann, D., Hall, A., Ruppert, C. & Bähler, M. (1995) A novel type of myosin implicated in signalling by rho family GTPases. EMBO.J. 14, 697-704. Wirth, J. A., Jensen, K. A., Post, P. L., Bement, W. M. & Mooseker, M. S. (1996) Human myosin-IXb, an unconventional myosin with a chimerin-like rho/rac GTPase-activating protein domain in its tail. J. Cell Sci. 109, 653-661.