The purpose of the studies proposed in this grant is to understand the molecular mechanisms underlying polarized targeting of neuronal transmembrane proteins.
The specific aims of this grant will concentrate on three main levels of polarized targeting: 1. Targeting of proteins at the plasma membrane through compartment-specific endocytosis and vesicle docking. 2. Trafficking of vesicles containing either axonal or dendritic proteins to the appropriate polarized compartment. 3. Sorting of axonal and dendritic proteins into separate vesicles. The ultimate goal of this research is to understand how these targeting mechanisms produce surface distributions of proteins that are highly polarized. Relevance Protein targeting plays an important role in many physiological processes such as the establishment and maintenance of synaptic connections. In addition, defects in trafficking are associated with numerous neurological diseases of major clinical significance such as Alzheimer's and Huntington's disease.

Public Health Relevance

In neurons many transmembrane proteins are targeted specifically to either the axonal or dendritic compartment. The goal of this grant is to understand the molecular mechanisms that mediate this targeting.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS041963-10
Application #
8288258
Study Section
Special Emphasis Panel (ZRG1-MDCN-F (03))
Program Officer
Silberberg, Shai D
Project Start
2001-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
10
Fiscal Year
2012
Total Cost
$347,288
Indirect Cost
$132,913
Name
University of Southern California
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Balasanyan, Varuzhan; Watanabe, Kaori; Dempsey, William P et al. (2017) Structure and Function of an Actin-Based Filter in the Proximal Axon. Cell Rep 21:2696-2705
Arnold, Don B; Gallo, Gianluca (2014) Structure meets function: actin filaments and myosin motors in the axon. J Neurochem 129:213-220
Mora, Rudy J; Roberts, Richard W; Arnold, Don B (2013) Recombinant probes reveal dynamic localization of CaMKII? within somata of cortical neurons. J Neurosci 33:14579-90
Watanabe, Kaori; Al-Bassam, Sarmad; Miyazaki, Yusuke et al. (2012) Networks of polarized actin filaments in the axon initial segment provide a mechanism for sorting axonal and dendritic proteins. Cell Rep 2:1546-53
Al-Bassam, Sarmad; Xu, Min; Wandless, Thomas J et al. (2012) Differential trafficking of transport vesicles contributes to the localization of dendritic proteins. Cell Rep 2:89-100
Lewis Jr, Tommy L; Mao, Tianyi; Arnold, Don B (2011) A role for myosin VI in the localization of axonal proteins. PLoS Biol 9:e1001021
Lewis Jr, Tommy L; Mao, Tianyi; Svoboda, Karel et al. (2009) Myosin-dependent targeting of transmembrane proteins to neuronal dendrites. Nat Neurosci 12:568-76
Arnold, Don B (2009) Actin and microtubule-based cytoskeletal cues direct polarized targeting of proteins in neurons. Sci Signal 2:pe49
Arnold, Don B (2007) Polarized targeting of ion channels in neurons. Pflugers Arch 453:763-9
Rivera, Jacqueline; Chu, Po-Ju; Lewis Jr, Tommy L et al. (2007) The role of Kif5B in axonal localization of Kv1 K(+) channels. Eur J Neurosci 25:136-46

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