Andrew Bean, Ph.D. | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston

Mechanisms of Vesicular Trafficking Including Neurotransmitter Secretion, Endocytosis, and Protein Sorting

Andrew J. Bean, Ph.D. - Assistant Professor The research in my laboratory is directed at understanding molecular mechanisms of vesicular trafficking and protein sorting. This fundamental process underlies synaptic transmission, which is critical for all brain processes and contributes to functions as basic as the development of neuronal architecture and learning/memory formation.

A model of how calcium may regulate the formation of fusogenic and nonfusogenic SNARE complexes to modulate the fusion of early endosomes. a, the concentration of calcium near two early endosomes is below that amount required to release Hrs from a SNARE complex with SNAP-25 and syntaxin 13. Fusion of the endosomes is blocked. b, an unknown trigger activates a calcium channel in an early endosome (one endosome shown for simplicity). The concentration of calcium rises locally to the point that causes Hrs to dissociate from the SNARE complex, most likely because of a putative conformational change. c, once calcium removes Hrs, VAMP-2 (or other SNARES) can then form a fusogenic SNARE complex with SNAP-25 and syntaxin 13, facilitating fusion of early endosomes. This model is based in part on a model describing how calcium might regulate vacuole fusion in yeast (Peters and Mayer 1998). [Click on image to view an enlarged version of the picture.]

Additionally, the mechanisms responsible for vesicular trafficking are also involved in viral (e.g., HIV) budding, and some types of cancer, underscoring the essential nature of this process.

Selected Reading

Sun, W, Yan, Q, Vida, TA, Bean, AJ. (2003) Hrs regulates early endosome fusion by inhibiting formation of an endosomal SNARE complex. J. Cell Biol. 162:125-137.

Yan, Q, Sun, W, McNew, JA, Vida, TA, Bean, AJ. (2004) Ca2+ and N-Ethylmaleimide-sensitive factor differentially regulate disassembly of SNARE complexes on early endosomes. J. Biol. Chem. 279:18270-18276.

Yan Q, Hunt PR, Frelin L, Vida TA, Pevsner J, Bean AJ. (2005) mVps24p functions in EGF receptor sorting/trafficking from the early endosome. Exp Cell Res. 304:265-73.

Yan Q, Sun W, Kujala P, Lotfi Y, Vida TA, Bean AJ. (2005) CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling. Mol Biol Cell. 16:2470-82.

Rayala SK, den Hollander P, Balasenthil S, Molli PR, Bean AJ, Vadlamudi RK, Wang RA, Kumar R. (2005) Hepatocyte growth factor regulated tyrosine kinase substrate (HRS) interacts with PELP1 and activates MAPK. J Biol Chem. Dec 12.

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