Don B. Arnold
Associate Professor, Biological Sciences, Division of Molecular Biology
Research Topics
- Ion channel
- Localization
- Neuron
- Confocal microscopy
Research Overview
The goal of my laboratory is to understand how ion channels are targeted to specific subcellular locations in neurons and how electrical activity can modulate that targeting. The physiological properties of a neuron are dependent not only on the properties of ion channels that it expresses, but also on their spatial distributions within that neuron. Little is known about how neurons maintain unique and often complex subcellular patterns of expression for each ion channel. Recently, we have identified two different peptide motifs, one in the coding sequence of a dendritic K+ channel, and a second in an axonal K+ channel, that mediate targeting to the respective compartments. In addition, we have identified the two kinesin motors that transport the channels, allowing us to study the interplay between kinesins and targeting motifs that results in subcellular trafficking. We are currently building on these results by asking the following questions: What are the differences between the secretory pathways taken by proteins that localize to dendrites vs. those of axonal proteins? Which proteins interact with axonal and dendritic targeting motifs and how do they mediate sorting into vesicles and trafficking of those vesicles? What mechanisms control the localization of proteins within subcellular compartments? For instance, what enables channels such as Kv4.2 and HCN-1 to assume a reverse gradient distribution within dendrites of hippocampal pyramidal cells? To address these questions we are using the following techniques: dissociated neuronal cultures or organotypic brain slices, confocal and 2-photon microscopy, and biochemistry.Contact Information
- Web Site:
- http://college.usc.edu/labs/arnold/home/index.cfm
- E-mail:
- darnold@usc.edu
- Mailing Address:
- University of Southern California
1050 Childs Way
Los Angeles, CA 90089-2910 - Office Location:
- RRI Bldg.Rm 204B
- Office Phone:
- (213) 821-1266
- Lab Location:
- RRI. Rm 208
- Lab Phone:
- (213) 821-1818
- Fax:
- (213) 821-1818
Education
- B.A.Sc. University of Toronto, 1986.
- Ph.D. John Hopkins University, 1992.
- Postdoctoral Fellow, Rockefeller University 1992-1997.
- Postdoctoral Fellow, Harvard University 1997-1999.
Research Images
Selected Publications
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Lewis TL Jr, Mao T, Svoboda K, Arnold DB. (2009) Myosin-dependent targeting of transmembrane proteins to neuronal dendrites. Nat Neurosci.12(5):568-576. -PubMed
Rivera J, Chu PJ, Lewis TL Jr, Arnold DB. (2007) The role of Kif5B in axonal localization of Kv1 K(+) channels. Eur J Neurosci. 25(1):136-146. -PubMed
Arnold DB. (2007) Polarized targeting of ion channels in neurons. Pflugers Arch. 453(6):763-769. -PubMed
Chu PJ, Rivera JF, Arnold DB. (2006) A role for Kif17 in transport of Kv4.2. J Biol Chem. 281(1):365-373. -PubMed
Rivera JF, Chu PJ, Arnold DB. (2005) The T1 domain of Kv1.3 mediates intracellular targeting to axons. Eur J Neurosci. 22(8):1853-1862. -PubMed
Rivera, J. F., Ahmad, S., Quick, M. W., Liman, E. R., and Arnold, D. B. (2003) An evolutionarily conserved dileucine motif in Shal K+ channels mediates dendritic targeting. Nat Neurosci. 6(3):243-250. -PubMed
Arnold DB. (1999) Clapham DE Molecular determinants for subcellular localization of PSD-95 with an interacting K+ channel. Neuron 23(1):149-157. -PubMed
Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME. (1998) Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20(4):709-726. -PubMed
Arnold DB, Heintz N. (1997) A calcium responsive element that regulates expression of two calcium binding proteins in Purkinje cells. Proc Natl Acad Sci USA 94(16):8842-8847. -PubMed
Arnold D, Feng L, Kim J, Heintz N. (1994) A strategy for the analysis of gene expression during neural development. Proc Natl Acad Sci USA 91(21):9970-9974. -PubMed