Alternative Splicing of the Human Rab6A Gene Generates Two Close but Functionally Different Isoforms
AUTOR(ES)
Echard, Arnaud
FONTE
The American Society for Cell Biology
RESUMO
Analysis of the human Rab6A gene structure reveals the presence of a duplicated exon, and incorporation of either of the two exons by alternative splicing is shown to generate two Rab6 isoforms named Rab6A and Rab6A′, which differ in only three amino acid residues located in regions flanking the PM3 GTP-binding domain of the proteins. These isoforms are ubiquitously expressed at similar levels, exhibit the same GTP-binding properties, and are localized to the Golgi apparatus. Overexpression of the GTP-bound mutants of Rab6A (Rab6A Q72L) or Rab6A′ (Rab6A′ Q72L) inhibits secretion in HeLa cells, but overexpression of Rab6A′ Q72L does not induce the redistribution of Golgi proteins into the endoplasmic reticulum. This suggests that Rab6A′ is not able to stimulate Golgi-to-endoplasmic reticulum retrograde transport, as described previously for Rab6A. In addition, Rab6A′ interacts with two Rab6A partners, GAPCenA and “clone 1,” but not with the kinesin-like protein Rabkinesin-6, a Golgi-associated Rab6A effector. Interestingly, we found that the functional differences between Rab6A and Rab6A′ are contingent on one amino acid (T or A at position 87). Therefore, limited amino acid substitutions within a Rab protein introduced by alternative splicing could represent a mechanism to generate functionally different isoforms that interact with distinct sets of effectors.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=15039Documentos Relacionados
- Alternative splicing generates secretory isoforms of human CD1.
- Alternative splicing of a Drosophila tropomyosin gene generates muscle tropomyosin isoforms with different carboxy-terminal ends.
- Alternative splicing of Pax-8 gene transcripts is developmentally regulated and generates isoforms with different transactivation properties.
- Alternative splicing in the human cytochrome P450IIB6 gene generates a high level of aberrant messages.
- The rat alpha-tropomyosin gene generates a minimum of six different mRNAs coding for striated, smooth, and nonmuscle isoforms by alternative splicing.