Calmodulin dissociation regulates Myo5 recruitment and function at endocytic sites.

Abstract

Myosins-I are conserved proteins that bear an N-terminal motor head followed by a Tail Homology 1 (TH1) lipid-binding domain. Some myosins-I have an additional C-terminal extension (C(ext)) that promotes Arp2/3 complex-dependent actin polymerization. The head and the tail are separated by a neck that binds calmodulin or calmodulin-related light chains. Myosins-I are known to participate in actin-dependent membrane remodelling. However, the molecular mechanisms controlling their recruitment and their biochemical activities in vivo are far from being understood. In this study, we provided evidence suggesting the existence of an inhibitory interaction between the TH1 domain of the yeast myosin-I Myo5 and its C(ext). The TH1 domain prevented binding of the Myo5 C(ext) to the yeast WIP homologue Vrp1, Myo5 C(ext)-induced actin polymerization and recruitment of the Myo5 C(ext) to endocytic sites. Our data also indicated that calmodulin dissociation from Myo5 weakened the interaction between the neck and TH1 domains and the C(ext). Concomitantly, calmodulin dissociation triggered Myo5 binding to Vrp1, extended the myosin-I lifespan at endocytic sites and activated Myo5-induced actin polymerization.

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Published Version (Please cite this version)

10.1038/emboj.2010.159

Publication Info

Grötsch, Helga, Jonathan P Giblin, Fatima-Zahra Idrissi, Isabel-María Fernández-Golbano, John R Collette, Thomas M Newpher, Virginia Robles, Sandra K Lemmon, et al. (2010). Calmodulin dissociation regulates Myo5 recruitment and function at endocytic sites. EMBO J, 29(17). pp. 2899–2914. 10.1038/emboj.2010.159 Retrieved from https://hdl.handle.net/10161/12467.

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Newpher

Thomas Mark Newpher

Associate Professor of the Practice of Psychology and Neuroscience

I teach, mentor, and advise for Duke's Undergraduate Studies in Neuroscience program, and serve as the Associate Director of Undergraduate Studies in Neuroscience. I also direct the Summer Neuroscience Program of Research in the Duke Institute for Brain Sciences. I earned my Ph.D. in molecular biology from Case Western Reserve University. After graduate school, I came to Duke University to receive postdoctoral training in the Neurobiology Department, where my research focused on identifying molecular mechanisms that underlie learning-related synaptic plasticity.

As the director of the Summer Neuroscience Program, I provide mentorship and professional development opportunities for undergraduate research fellows. My courses use a variety of team-based learning activities to promote critical thinking skills, foster collaboration among students, and create an engaging, student-centered classroom experience. As a co-PI in the Duke Team-Based Learning lab, I study the impacts of collaborative learning on student performance and classroom dynamics.


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