Regulatory implications of non-trivial splicing: Isoform 3 of Rab1A shows enhanced basal activity and is not controlled by accessory proteins

Patricia Schöppner, Gergely Csaba, Tatjana Braun, Marina Daake, Bettina Richter, Oliver F. Lange, Martin Zacharias, Ralf Zimmer, Martin Haslbeck

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Alternative splicing often affects structured and highly conserved regions of proteins, generating so called non-trivial splicing variants of unknown structure and cellular function. The human small G-protein Rab1A is involved in the regulation of the vesicle transfer from the ER to Golgi. A conserved non-trivial splice variant lacks nearly 40% of the sequence of the native Rab1A, including most of the regulatory interaction sites. We show that this variant of Rab1A represents a stable and folded protein, which is still able to bind nucleotides and co-localizes with membranes. Nevertheless, it should be mentioned that compared to other wild-typeRabGTPases, the measured nucleotide binding affinities are dramatically reduced in the variant studied. Furthermore, the Rab1A variant forms hetero-dimers with wild-type Rab1A and its presence in the cell enhances the efficiency of alkaline phosphatase secretion. However, this variant shows no specificity for GXP nucleotides, a constantly enhanced GTP hydrolysis activity and is no longer controlled by GEF or GAP proteins, indicating a new regulatory mechanism for the Rab1A cycle via alternative non-trivial splicing.

Original languageEnglish
Pages (from-to)1544-1557
Number of pages14
JournalJournal of Molecular Biology
Volume428
Issue number8
DOIs
StatePublished - 24 Apr 2016
Externally publishedYes

Keywords

  • Rab1A
  • non-trivial splicing
  • protein folding
  • protein secretion

Fingerprint

Dive into the research topics of 'Regulatory implications of non-trivial splicing: Isoform 3 of Rab1A shows enhanced basal activity and is not controlled by accessory proteins'. Together they form a unique fingerprint.

Cite this