Study of the human orthologues of the yeast ELC Mlc1p

Myosin V are actin-based motors required for short-range transport of various organelles and mRNAs. The human genome encodes three MyoVs. Mutation of MyoVa or MyoVb results in Griscelli syndrome type 1 and the Microvillus Inclusion Disease, respectively. Understanding how MyoVs are co-regulated will clarify the clinical manifestation of MyoV-related syndromes. MyoV is composed of two myosin heavy chains (MHCs) to which different Myosin Light Chains (Calmodulin and Essential Light Chain) associate. They bind with different specificity to IQ motifs present in the MHC neck domain. The ELC composition of MyoV has been poorly studied in vivo, but their heterogeneity and structural specificity suggest a specific function in regulating MyoVs. The budding yeast ELC Mlc1p is essential for cytokinesis and associates, together with calmodulin, with the MyoV Myo2p. Unlike calmodulin it does not bind calcium. So far only the fission yeast orthologue, Cdc4p, has been shown to belong to this class of ELC. We used structural, yeast genetic and biochemical tools to identify the human loci encoding Mlc1-type ELCs. Studies are ongoing aimed at clarifying their function in epithelial and neuronal cell types