Document Detail

Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation.
MedLine Citation:
PMID:  15780940     Owner:  NLM     Status:  MEDLINE    
The activation of Rab GTPases is a critical focal point of membrane trafficking events in eukaryotic cells; however, the cellular mechanisms that spatially and temporally regulate this process are poorly understood. Here, we identify a null allele of ELP1 as a suppressor of a mutant in a Rab guanine nucleotide exchange factor Sec2p. Elp1p was previously thought to be involved in transcription elongation as part of the Elongator complex. We show that elp1Delta suppression of sec2(ts) is not a result of reduced transcriptional elongation and that Elp1p physically associates with Sec2p. The Sec2p interaction domain of Elp1p is necessary for both Elp1p function and for the polarized localization of Sec2p. Mutations in human Elp1p (IKAP) are a known cause of familial dysautonomia (FD). Our results raise the possibility that regulation of polarized exocytosis is an evolutionarily conserved function of the entire Elongator complex and that FD results from a dysregulation of neuronal exocytosis.
Peter B Rahl; Catherine Z Chen; Ruth N Collins
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Molecular cell     Volume:  17     ISSN:  1097-2765     ISO Abbreviation:  Mol. Cell     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-22     Completed Date:  2005-04-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  841-53     Citation Subset:  IM    
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
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MeSH Terms
Amino Acid Sequence
Cell Nucleus / metabolism
Cell Polarity
Cytoplasm / metabolism
Dysautonomia, Familial / genetics
GTP-Binding Proteins / genetics,  metabolism*
Gene Expression Regulation, Fungal*
Guanine Nucleotide Exchange Factors
Histone Acetyltransferases
Molecular Sequence Data
Mutation / genetics
Peptide Elongation Factors / genetics,  metabolism*
Saccharomyces cerevisiae / cytology,  genetics,  metabolism*
Saccharomyces cerevisiae Proteins / genetics,  metabolism*
Transcription, Genetic / genetics*
Reg. No./Substance:
0/Guanine Nucleotide Exchange Factors; 0/Peptide Elongation Factors; 0/SEC2 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; EC Acetyltransferases; EC protein, S cerevisiae; EC 3.6.1.-/GTP-Binding Proteins

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