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 endocytic mechanisms responsible for sorting membrane proteins are also involved in viral (e.g., HIV) budding, and some types of cancer, underscoring the essential nature of this process.
Cell-Free Reconstitution of Multivesicular Body Formation and Receptor Sorting. Sun W, Vida TA, Sirisaengtaksin N, Merrill SA, Hanson PI, Bean AJ. Traffic. 2010 Feb 27. PMID: 20214752
Rapid recycling of beta-adrenergic receptors is dependent on the actin cytoskeleton and myosin Vb. Millman EE, Zhang H, Zhang H, Godines V, Bean AJ, Knoll BJ, Moore RH. Traffic. 2008 Nov;9(11):1958-71. PMID: 18785920
The endosome-associated protein Hrs is hexameric and controls cargo sorting as a "master molecule". Pullan L, Mullapudi S, Huang Z, Baldwin PR, Chin C, Sun W, Tsujimoto S, Kolodziej SJ, Stoops JK, Lee JC, Waxham MN, Bean AJ, Penczek PA. Structure. 2006 Apr;14(4):661-71.PMID: 16615908
Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) interacts with PELP1 and activates MAPK. Rayala SK, Hollander P, Balasenthil S, Molli PR, Bean AJ, Vadlamudi RK, Wang RA, Kumar R. J Biol Chem. 2006 Feb 17;281(7):4395-403. PMID: 16352611
CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling. Yan Q, Sun W, Kujala P, Lotfi Y, Vida TA, Bean AJ. Mol Biol Cell. 2005 May;16(5):2470-82. PMID: 15772161
mVps24p functions in EGF receptor sorting/trafficking from the early endosome. Yan Q, Hunt PR, Frelin L, Vida TA, Pevsner J, Bean AJ. Exp Cell Res. 2005 Mar 10;304(1):265-73. PMID: 15707591
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