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.
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.
|Arnold, Don B; Gallo, Gianluca (2014) Structure meets function: actin filaments and myosin motors in the axon. J Neurochem 129:213-20|
|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|
|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|
|Chu, Po-Ju; Rivera, Jacqueline F; Arnold, Don B (2006) A role for Kif17 in transport of Kv4.2. J Biol Chem 281:365-73|
|Rivera, Jacqueline F; Chu, Po-Ju; Arnold, Don B (2005) The T1 domain of Kv1.3 mediates intracellular targeting to axons. Eur J Neurosci 22:1853-62|
|Rivera, Jacqueline F; Ahmad, Shoeb; Quick, Michael W et al. (2003) An evolutionarily conserved dileucine motif in Shal K+ channels mediates dendritic targeting. Nat Neurosci 6:243-50|