Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation

Peter B Rahl; Catherine Z Chen; Ruth N Collins

doi:10.1016/j.molcel.2005.02.018

Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation

Mol Cell. 2005 Mar 18;17(6):841-53. doi: 10.1016/j.molcel.2005.02.018.

Authors

Peter B Rahl¹, Catherine Z Chen, Ruth N Collins

Affiliation

¹ Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.

PMID: 15780940
DOI: 10.1016/j.molcel.2005.02.018

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amino Acid Sequence
Cell Nucleus / metabolism
Cell Polarity
Cytoplasm / metabolism
Dysautonomia, Familial / genetics
Exocytosis*
GTP-Binding Proteins / genetics
GTP-Binding Proteins / metabolism*
Gene Expression Regulation, Fungal*
Guanine Nucleotide Exchange Factors
Histone Acetyltransferases
Humans
Molecular Sequence Data
Mutation / genetics
Peptide Elongation Factors / genetics
Peptide Elongation Factors / metabolism*
Saccharomyces cerevisiae / cytology
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Transcription, Genetic / genetics*

Substances

Guanine Nucleotide Exchange Factors
Peptide Elongation Factors
SEC2 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
Histone Acetyltransferases
IKI3 protein, S cerevisiae
GTP-Binding Proteins