QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 23, 2003, 23(16):6537-6545

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (18) Citing Articles via Google Scholar Google Scholar Articles by Mathews, E. A. Articles by Snutch, T. P. Search for Related Content PubMed PubMed Citation Articles by Mathews, E. A. Articles by Snutch, T. P.

 Previous Article  |  Next Article 

Critical Residues of the Caenorhabditis elegans unc-2 Voltage-Gated Calcium Channel That Affect Behavioral and Physiological Properties

Eleanor A. Mathews,¹ Esperanza García,¹ Celia M. Santi,¹ Gregory P. Mullen,² Colin Thacker,¹ Donald G. Moerman,² and Terrance P. Snutch¹

¹Biotechnology Laboratory and ²Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3

The Caenorhabditis elegans unc-2 gene encodes a voltage-gated calcium channel ₁ subunit structurally related to mammalian dihydropyridine-insensitive high-threshold channels. In the present paper we describe the characterization of seven alleles of unc-2. Using an unc-2 promoter-tagged green fluorescent protein construct, we show that unc-2 is primarily expressed in motor neurons, several subsets of sensory neurons, and the HSN and VC neurons that control egg laying. Examination of behavioral phenotypes, including defecation, thrashing, and sensitivities to aldicarb and nicotine suggests that UNC-2 acts presynaptically to mediate both cholinergic and GABAergic neurotransmission. Sequence analysis of the unc-2 alleles shows that e55, ra605, ra606, ra609, and ra610 all are predicted to prematurely terminate and greatly reduce or eliminate unc-2 function. In contrast, the ra612 and ra614 alleles are missense mutations resulting in the substitution of highly conserved residues in the C terminus and the domain IVS4-IVS5 linker, respectively. Heterologous expression of a rat brain P/Q-type channel containing the ra612 mutation shows that the glycine to arginine substitution affects a variety of channel characteristics, including the voltage dependence of activation, steady-state inactivation, as well as channel kinetics. Overall, our findings suggest that UNC-2 plays a pivotal role in mediating a number of physiological processes in the nematode and also defines a number of critical residues important for calcium channel function in vivo.

Key words: calcium channel; mutation; behavior; electrophysiology; presynaptic; C. elegans

---

Received Dec. 4, 2002; revised May. 22, 2003; accepted May. 22, 2003.

This article has been cited by other articles:

				R. Branicky and S. Hekimi Specification of muscle neurotransmitter sensitivity by a Paired-like homeodomain protein in Caenorhabditis elegans Development, November 15, 2005; 132(22): 4999 - 5009. [Abstract] [Full Text] [PDF]

				T. Umemura, P. Rapp, and C. Rongo The role of regulatory domain interactions in UNC-43 CaMKII localization and trafficking J. Cell Sci., August 1, 2005; 118(15): 3327 - 3338. [Abstract] [Full Text] [PDF]

				G. Jiang, L. Zhuang, S. Miyauchi, K. Miyake, Y.-J. Fei, and V. Ganapathy A Na+/Cl--coupled GABA Transporter, GAT-1, from Caenorhabditis elegans: STRUCTURAL AND FUNCTIONAL FEATURES, SPECIFIC EXPRESSION IN GABA-ERGIC NEURONS, AND INVOLVEMENT IN MUSCLE FUNCTION J. Biol. Chem., January 21, 2005; 280(3): 2065 - 2077. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help