SECRETORY PATHWAY REGULATION Transcription Regulator Moonlights in Polarized Secretion

The Elongator complex of six proteins is thought to regulate transcription elongation in yeast, although detection of three components in the cytosol has raised questions about additional functions. Rahl et al. have determined that the Elongator protein Elp1p regulates vesicular trafficking in yeast. Elp1p was identified in a screen based on a yeast mutant with a secretion defect due to a mutation in the SEC2 gene. The corresponding protein, Sec2p, is a guanine nucleotide exchange factor that activates Sec4p, a Rab family GTPase that controls yeast exocytosis. Elp1p negatively regulates Sec2p function and polarized secretion through the Sec2p/Sec4-mediated pathway. Removal of Elp1p expression increased Sec4p activation and secretion. Elp1p directly associates with Sec2p, as determined by a yeast two-hybrid assay, coimmunoprecipitation from yeast lysates, and association of purified proteins. Sec2p is a cytosolic protein that concentrates to sites of exocytosis. Loss of Sec2p interaction with the C terminus of Elp1p resulted in loss of Sec2p localization and function. Thus, two seemingly separate cellular processes, transcription and membrane trafficking, may share a common regulatory mechanism. The mammalian homolog of Elp1p is IKK-complex associated protein (IKAP), a component of the nuclear factor B (NF-B) signaling pathway. Mutations in IKAP associated with the neurodegenerative disease familial dysautonomia may be linked to defective exocytosis in neurons.

P. B. Rahl. C. Z. Chen, R. N. Collins, Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation. Mol. Cell 17, 841-853 (2005). [PubMed]