Structural highlights
Function
[MYO7B_HUMAN] Myosins are actin-based motor molecules with ATPase activity. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length. May link the complex to the actin core bundle of microvilli (Probable).[1] [2]
Publication Abstract from PubMed
Cadherin linkages between adjacent stereocilia and microvilli are essential for mechanotransduction and maintaining their organization. They are anchored to actin through interaction of their cytoplasmic domains with related tripartite complexes consisting of a class VII myosin and adaptor proteins: Myo7a/SANS/Harmonin in stereocilia and Myo7b/ANKS4B/Harmonin in microvilli. Here, we determine high-resolution structures of Myo7a and Myo7b C-terminal MyTH4-FERM domain (MF2) and unveil how they recognize harmonin using a novel binding mode. Systematic definition of interactions between domains of the tripartite complex elucidates how the complex assembles and prevents possible self-association of harmonin-a. Several Myo7a deafness mutants that map to the surface of MF2 disrupt harmonin binding, revealing the molecular basis for how they impact the formation of the tripartite complex and disrupt mechanotransduction. Our results also suggest how switching between different harmonin isoforms can regulate the formation of networks with Myo7a motors and coordinate force sensing in stereocilia.
Myosin 7 and its adaptors link cadherins to actin.,Yu IM, Planelles-Herrero VJ, Sourigues Y, Moussaoui D, Sirkia H, Kikuti C, Stroebel D, Titus MA, Houdusse A Nat Commun. 2017 Jun 29;8:15864. doi: 10.1038/ncomms15864. PMID:28660889[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Crawley SW, Shifrin DA Jr, Grega-Larson NE, McConnell RE, Benesh AE, Mao S, Zheng Y, Zheng QY, Nam KT, Millis BA, Kachar B, Tyska MJ. Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion. Cell. 2014 Apr 10;157(2):433-46. doi: 10.1016/j.cell.2014.01.067. PMID:24725409 doi:http://dx.doi.org/10.1016/j.cell.2014.01.067
- ↑ Crawley SW, Weck ML, Grega-Larson NE, Shifrin DA Jr, Tyska MJ. ANKS4B Is Essential for Intermicrovillar Adhesion Complex Formation. Dev Cell. 2016 Jan 25;36(2):190-200. doi: 10.1016/j.devcel.2015.12.022. PMID:26812018 doi:http://dx.doi.org/10.1016/j.devcel.2015.12.022
- ↑ Yu IM, Planelles-Herrero VJ, Sourigues Y, Moussaoui D, Sirkia H, Kikuti C, Stroebel D, Titus MA, Houdusse A. Myosin 7 and its adaptors link cadherins to actin. Nat Commun. 2017 Jun 29;8:15864. doi: 10.1038/ncomms15864. PMID:28660889 doi:http://dx.doi.org/10.1038/ncomms15864
