File(s) not publicly available

Novel splice variants of Rat CaV2.1 that lack much of the synaptic protein interaction site are expressed in neuroendocrine cells

journal contribution
posted on 06.12.2017, 00:00 authored by W Kosala, D Wang, Jonathan DaviesJonathan Davies, L Chen, G Zamponi, T Fisher, J Rajapaksha
Voltage-gated Ca(2+) channels are responsible for the activation of the Ca(2+) influx that triggers exocytotic secretion. The synaptic protein interaction (synprint) site found in the II-III loop of Ca(V)2.1 and Ca(V)2.2 mediates a physical association with synaptic proteins that may be crucial for fast neurotransmission and axonal targeting. We report here the use of nested PCR to identify two novel splice variants of rat Ca(V)2.1 that lack much of the synprint site. Furthermore, we compare immunofluorescence data derived from antibodies directed against sequences in the Ca(V)2.1 synprint site and carboxyl terminus to show that channel variants lacking a portion of the synprint site are expressed in two types of neuroendocrine cells. Immunofluorescence data also suggest that such variants are properly targeted to neuroendocrine terminals. When expressed in a mammalian cell line, both splice variants yielded Ca(2+) currents, but the variant containing the larger of the two deletions displayed a reduced current density and a marked shift in the voltage dependence of inactivation. These results have important implications for Ca(V)2.1 function and for the mechanisms of Ca(V)2.1 targeting in neurons and neuroendocrine cells.

Funding

Category 2 - Other Public Sector Grants Category

History

Volume

283

Issue

23

Start Page

15997

End Page

16003

Number of Pages

7

eISSN

1083-351X

ISSN

0021-9258

Language

en-aus

Peer Reviewed

Yes

Open Access

No

External Author Affiliations

TBA Research Institute; University of Calgary; University of Saskatchewan;

Era Eligible

Yes

Journal

Journal of biological chemistry.