The SNARE protein vti1a functions in dense-core vesicle biogenesis

Alexander M Walter, Julia Kurps, Heidi de Wit, Susanne Schöning, Trine L Toft-Bertelsen, Juliane Lauks, Iwona Ziomkiewicz, Annita N Weiss, Alexander Schulz, Gabriele Fischer von Mollard, Matthijs Verhage, Jakob Balslev Sørensen

Research output: Contribution to journalJournal articleResearchpeer-review

32 Citations (Scopus)

Abstract

The SNARE protein vti1a is proposed to drive fusion of intracellular organelles, but recent data also implicated vti1a in exocytosis. Here we show that vti1a is absent from mature secretory vesicles in adrenal chromaffin cells, but localizes to a compartment near the trans-Golgi network, partially overlapping with syntaxin-6. Exocytosis is impaired in vti1a null cells, partly due to fewer Ca(2+)-channels at the plasma membrane, partly due to fewer vesicles of reduced size and synaptobrevin-2 content. In contrast, release kinetics and Ca(2+)-sensitivity remain unchanged, indicating that the final fusion reaction leading to transmitter release is unperturbed. Additional deletion of the closest related SNARE, vti1b, does not exacerbate the vti1a phenotype, and vti1b null cells show no secretion defects, indicating that vti1b does not participate in exocytosis. Long-term re-expression of vti1a (days) was necessary for restoration of secretory capacity, whereas strong short-term expression (hours) was ineffective, consistent with vti1a involvement in an upstream step related to vesicle generation, rather than in fusion. We conclude that vti1a functions in vesicle generation and Ca(2+)-channel trafficking, but is dispensable for transmitter release.

Original languageEnglish
JournalE M B O Journal
Volume33
Pages (from-to)1681-1697
Number of pages16
ISSN0261-4189
DOIs
Publication statusPublished - 5 Jun 2014

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