Reichhart, Nadine and Markowski, Magdalena and Ishiyama, Shimpei and Wagner, Andrea and Crespo-Garcia, Sergio and Schorb, Talitha and Ramalho, Jose S. and Milenkovic, Vladimir M. and Foeckler, Renate and Seabra, Miguel C. and Strauss, Olaf (2015) Rab27a GTPase modulates L-type Ca2+ channel function via interaction with the II-III linker of Ca(V)1.3 subunit. CELLULAR SIGNALLING, 27 (11). pp. 2231-2240. ISSN 0898-6568, 1873-3913
Full text not available from this repository. (Request a copy)Abstract
In a variety of cells, secretory processes require the activation of both Rab27a and L-type channels of the Ca(V)1.3 subtype. In the retinal pigment epithelium (RPE), Rab27a and Ca(V)1.3 channels regulate growth-factor secretion towards its basolateral side. Analysis of murine retina sections revealed a co-localization of both Rab27a and Ca(V)1.3 at the basolateral membrane of the RPE. Heterologously expressed Ca(V)1.3/beta 3/alpha(2)delta(1) channels showed negatively shifted voltage-dependence and decreased current density of about 70% when co-expressed with Rab27a. However, co-localization analysis using alpha(5)beta(1) integrin as a membrane marker revealed that Rab27a co-expression reduced the surface expression of Ca(V)1.3 only about 10%. Physical binding of heterologously expressed Rab27a with Ca(V)1.3 channels was shown by co-localization in immunocytochemistry as well as co-immunoprecipitation which was abolished after deletion of a MyRIP-homologous amino acid sequence at the II-III linker of the Ca(V)1.3 subunit. Rab27a over-expression in ARPE-19 cells positively shifted the voltage dependence, decreased current density of endogenous Ca(V)1.3 channels and reduced VEGF-A secretion. We show the first evidence of a direct functional modulation of an ion channel by Rab27a suggesting a new mechanism of Rab and ion channel interaction in the control of VEGF-A secretion in the RPE. (C) 2015 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; CORE VESICLE EXOCYTOSIS; TRANSMEMBRANE CONDUCTANCE REGULATOR; NATIVE KV1.3 CHANNELS; CALCIUM-CHANNELS; CHLORIDE CHANNEL; MEMBRANE; PROTEIN; EFFECTOR; Rab GTPase; Rab27a; Ca(v)1.3; Protein interaction; Voltage dependence; MyRIP |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 May 2019 12:59 |
| Last Modified: | 13 May 2019 12:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4582 |
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