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CAREER:Determine the mechanical properties of molecular motors in vesicle transports

$692,792FY2015BIONSF

Wayne State University, Detroit MI

Investigators

Abstract

An essential cellular process indispensable for life is the transport of molecules such as vesicles, mRNA, and protein complexes. Class V myosin proteins are molecular motors that transport such molecules along actin filaments in cells. An important property of the motor proteins is their ability to walk processively, which means that they move along their protein tracks without dissociating from the track. While other myosin V isoforms are well studied, the mechanism underlying myosin Vc motility, an important vertebrate motor, is not well understood. This project studies a novel molecular movement in live cells by which non-processive molecular motors like myosin Vc may demonstrate processive activities by clustering and working together. The project offers an interdisciplinary training opportunity for undergraduate and graduate students (including members of underrepresented groups) who will conduct state-of-the-art microscopy, as well as biochemistry and molecular biology experiments combined with computational modeling. Students will have opportunities to present their work at national and international conferences. In addition, the PI reaches out to the high-school students and teachers in the Detroit Public Schools, through the Light Microscope Summer program with the aim to disseminate his research to the public at large in order to educate the next generation of interdisciplinary scientists. Cargo transport is an essential cellular process indispensable for life across phylogeny. The processivity, which is the key physical factor to determine the directed intracellular transport efficiency of molecular motors, has been extensively studied at the single molecule level. However, the possibility that non-processive molecular motors demonstrate processive activities by forming multimers remains largely unaddressed. Using single-molecule and protein-engineering techniques, the project studies the novel and unique mechanistic movement of myosin Vc multimers. This work has the potential to uncover a new paradigm regarding directed molecular movement, that is, non-processive molecular motors like myosin Vc may demonstrate processive activities by clustering and working together in order to provide directional molecular transport in cells. The results of this project may have wider applicability by providing basic elements for the design of nanomotors with controllable transport properties.

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