Unconventional secretion of tubby and tubby-like protein 1.
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.
Caberoy
Nora B
NB
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, Miami, FL 33136, USA.
Li
Wei
W
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002451:Cell Compartmentation; D005136:Eye Proteins / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D051379:Mice; D009154:Mutation; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D011506:Proteins; C098988:Tub protein, mouse; C491353:Tulp1 protein, mouse; D016222:Fibroblast Growth Factor 2
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