Myosin III (nina C)

Pages updated 13th Nov '03

First described from Drosophila melanogaster as nina C (neither inactivation nor after potential), in a photo-transduction mutant screen.  Myosin III is a divergent myosin member, even within the myosin head domain, with a ~ 300 a.a. kinase -like domain at the N-terminus.  A homolog has been identified in the Limulus eye a (fellow arthropod) (Battelle et al, 2001), in fish (Hillman et al, 1996), possibly Octopus (DeVelasco et al, 1999), and a myosin III homolog has been discovered through the human genome project (Berg et al, 2001), and cloned (Dose & Burnside, 2000),  but no information is yet available on tissue expression. Myosin III is part of a signalling complex and is required for the adaptation response (reviewed in Bähler, 2000) that binds actin in an ATP sensitive manner (Hicks et al, 1996; Dose et al, 2003), and performs plus-end directed motor function (Komaba et al, 2003).  Consistent with this motor activity, myosin III is located at the peripheral extremities of filopod in transfected HeLa cells, and this does not occur in myosin IIIs with motor activity mutations (Les Erickson et al, 2003).

A.  Two forms of NinaC are expressed by differential splicing of the same gene in Drosophila.

B.  The structure of vertebrate (striped sea bass) Myosin III iso-forms.  

Myosin III and human disease
Human myosin III has been implicated as a potential candidate for Bardet-Biedl syndrome (so has Myosin IX) (Dose & Burnside, 2002), and mutation in the myosin IIIA gene, has been reported to cause a non-syndromic hearing loss (Walsh et al, 2002). Curiously, this deafness does not result in loss of vision even though myosin IIIA is expressed in retina (Dose & Burnside, 2000), however it is possible that myosin IIIB compensates for loss of myosin IIIA function as a myosin IIIB cDNA (AF369908) has been identified in human retina.  Another possibility is that the particular mutations that cause deafness do not affect the particular function of the protein in the retina.

Myosin III function
It is not at all clear what myosin III does or how it does it.  In the vertebrate eye myosin III is localised to the actin filament bundles in the photoreceptors in a structure known as the calycal process, a microvillus like structure at the base of the outer segments (Dose et al, 2003).  For a long time after its discovery no motor activity was detected in myosin III and in fact the important P loop (the ATP binding loop in the motor head) is substantially different in Nina C made it questionable if this myosin is a motor.  However it has now (Komaba et al, 2003) been reported that human myosin III has a plus end directed, actin-based  motor activity. The Drosophila eye has provided almost all the known in vivo details so far (Porter et al, 1993; Porter & Montell, 1993).

References:-

Bähler, M. (2000) Are class III and class IX myosins motorized signalling molecules? BBA. 1496, 52-59.

Battelle, B. A., Dabdoub, A., Malone, M. A., Andrews, A. W., Cacciatore, C., Calman, B. G., Smith, W. C. & Payne, R. (2001) Immunocytochemical localization of opsin, visual arrestin, myosin III, and calmodulin in Limulus lateral eye retinular cells and ventral photoreceptors. J. Comp. Neurol. 435, 211-215.

Berg, J. S., Powell, B. C. & Cheney, R. E. (2001) A millennial myosin census. Mol.Biol.Cell. 12, 780-794.

De Velasco, B., Martinez, J. M., Ochoa, G. H., Miller, A. M., Clark, Y. M., Matsumoto, B. & Robles, L. J. (1999) Identification and immunolocalization of actin cytoskeletal components in light- and dark-adapted octopus retinas. Exp.Eye Res. 68, 725-737.

Dose, A. C. & Burnside, B. (2000) Cloning and chromosomal localization of a human class III myosin. Genomics. 67, 333-342.

Dose, A. C. & Burnside, B. (2002) A Class III Myosin Expressed in the Retina Is a Potential Candidate for Bardet-Biedl Syndrome. Genomics. 79, 621-624.

Dose, A. C., Hillman, D. W., Wong, C., Sohlberg, L., Lin-Jones, J. & Burnside, B. (2003) Myo3A, One of Two Class III Myosin Genes Expressed in Vertebrate Retina, Is Localized to the Calycal Processes of Rod and Cone Photoreceptors and Is Expressed in the Sacculus.  Mol. Biol. Cell. 14, 1058-1073.

Hicks, J. L., Liu, X. & Williams, D. S. (1996) Role of the ninaC proteins in photoreceptor cell structure: ultrastructure of ninaC deletion mutants and binding to actin filaments. Cell Motility Cytoskeleton. 35, 367-379.

Hillman, D., Bost-Usinger, L. & Burnside, B. (1996) A potential vertebrate homologue of Drosophila ninaC. Mol.Biol. Cell. 7, 3a.

Komaba, S., Inoue, A., Maruta, S., Hosoya, H. & Ikebe, M. (2003) Determination of Human Myosin III as a Motor Protein Having a Protein Kinase Activity.  J. Biol. Chem. 278, 21352-21360.

Les Erickson, F., Corsa, A. C., Dose, A. C. & Burnside, B. (2003) Localization of a Class III Myosin to Filopodia Tips in Transfected HeLa Cells Requires an Actin-binding Site in its Tail Domain, Mol. Biol. Cell. 14, 4173-4180.

Li, H. S., Porter, J. A. & Montell, C. (1998) Requirement for the NINAC kinase/myosin for stable termination of the visual cascade. J.Neurosci. 18, 9601-9606.

Porter, J. A., Yu, M., Doberstein, S. K., Pollard, T. D. & Montell, C. (1993) Dependence of calmodulin localization in the retina on the NINAC unconventional myosin. Science. 262, 1038-1042.

Porter, J. A. & Montell, C. (1993) Distinct roles of the Drosophila ninaC kinase and myosin domains revealed by systematic mutagenesis. J.Cell Biol. 122, 601-612.

Walsh, T., Walsh, V., Vreugde, S., Hertzano, R., Shahin, H., Haika, S., Lee, M. K., Kanaan, M., King, M.-K. & Avraham, K. B. (2002) From flies' eyes to our ears: Mutations in a human class III myosin cause progressive nonsyndromic hearing loss DFNB30. PNAS. 99, 7518-7523.