Unconventional secretion of tubby and tubby-like protein 1.

Nora B Caberoy, Wei Li

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, Miami, FL 33136, USA.

FEBS letters 2009 Sep 17

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Tubby-like proteins (Tulps) with no signal peptide have been characterized as cytoplasmic proteins with various intracellular functions, including binding to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2)]. PI(4,5)P(2) has been implicated in unconventional secretion of fibroblast growth factor-2 without a signal peptide. Here, we show that all Tulps are expressed intracellularly and extracellularly. Tubby secretion is partially dependent on its PI(4,5)P(2)-binding activity with an essential secretory signal in the N-terminus. Pathogenic mutation in Tubby mice has no impact on tubby extracellular trafficking. Moreover, unconventional secretion of tubby and Tulp1 is independent of endoplasmic reticulum-Golgi pathway. These data implicate that Tulps may function extracellularly as well.