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Title:Regulation of Organelle Transport by Myosin v in the Cell Cycle
Author(s):Karcher, Ryan Lee
Doctoral Committee Chair(s):Vladimir I. Gelfand
Department / Program:Microbiology
Discipline:Microbiology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Biology, Cell
Abstract:Eukaryotic cells utilize motor proteins to transport cargo to their correct intracellular destinations and compartmentalize the cytoplasm. While the list of motor proteins and their cargo continues to expand, little is known about the regulation of motor-cargo association. Xenopus laevis melanophores are a convenient model system in which to study intracellular transport. The movement of pigmented organelles in these cells is controlled by three motors: two microtublule motors, cytoplasmic dynein and kinesin II, and the actin motor myosin V. Here, the cell cycle regulation of myosin V was investigated. In earlier work from our lab, myosin V was found to be downregulated, as it was released from organelles during mitosis [Rogers et al., J Cell Biol. 146, 1265 (1999)]. This release also correlated to an increase in the mitotic phosphorylation of the motor's heavy chain. To determine if this correlation was a causal relationship, the mitotic phosphorylation site in the motor's tail was first identified by multidimensional mass spectrometry analysis, and then mutated to study its functionality [Karcher et al., Science. 293, 1317 (2001)]. The phosphorylated residue, Ser1650, was found to comprise the molecular switch for motor release and, therefore, downregulates myosin V during mitosis. In addition, CaMKII was found to specifically phosphorylate Ser1650 in vitro and also regulated motor binding to the organelle. This is the first demonstration of a cell cycle dependent regulation of an actin motor to our knowledge.
Issue Date:2003
Type:Text
Language:English
Description:51 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2003.
URI:http://hdl.handle.net/2142/86654
Other Identifier(s):(MiAaPQ)AAI3101880
Date Available in IDEALS:2015-09-28
Date Deposited:2003


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