Professor, Neurobiology & Anatomy
About Dr. Bean
Dr. Bean was born in the Netherlands and was academically trained at Oberlin, Yale, Karolinska Institute, and Stanford. He has been on faculty at the University of Texas Medical School since 1997.
Molecular Mechanisms Of Endocytic Protein Sorting
Plasma membrane resident proteins (receptors, channels, transporters) perform diverse functions that drive cellular reactions to extracellular signals. To adapt in a changing environment, cells may fine-tune their responses by regulating the number of proteins present at the cell surface. Removal of membrane proteins from the plasma membrane by endocytosis follows a canonical itinerary in which cargo passes through morphologically and biochemically defined organelles. Not all membrane proteins that enter the endocytic pathway are degraded in the lysosome. During transit through the endocytic pathway proteins are sorted for movement to a variety of compartments. A critical step that determines whether a protein will be degraded occurs when that protein is, or is not, internalized into the internal vesicles of the late endosome/mutlivesicular body (MVB), an organelle containing internal vesicles formed by the invagination of its limiting membrane. Cytosolic protein complexes (ESCRTs) mediate cargo movement from the limiting membrane of the MVB into internal vesicles. ESCRTs can only recognize, bind to, and sort proteins that have been tagged with ubiquitin. Untagged proteins remain on the endocytic membrane, for recycling to the cell surface or movement to other compartments. MVBs may fuse with lysosomes, resulting in degradation of cargo that has been sorted into internal vesicles, or they may fuse with the plasma membrane resulting in secretion of exosomes, the internal vesicles that may be involved in intracellular communication.
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. The endocytic mechanisms responsible for sorting membrane proteins are also involved in viral (e.g., HIV) budding, and cancers, underscoring the essential nature of this process.
- Cell-free reconstitution of multivesicular body (MVB) cargo sorting. Gireud M, Sirisaengtaksin N, Tsunoda S, Bean AJ. Methods Mol Biol. 2015; 1270:115-24. doi: 10.1007/978-1-4939-2309-0_9.
- Etoposide-loaded immunoliposomes as active targeting agents for GD2 positive malignancies. Brown, B.S., Patanam, T., Mobli, K., Celia, C., Zage, P.E., Bean, A.J.*, Tasciotti, E., Cancer Biology and Therapy, 15:1-11, 2014 PMID: 24755919.
- UBE4B couples ubiquitination and sorting machineries to enable EGFR degradation.Sirisaengtaksin N, Gireud M, Yan Q, Kubota Y, Meza D, Waymire JC, Zage PE, Bean AJ. Journal of Biological Chemistry. 2014 Jan 31; 289(5):3026-39. PMID:24344129.
- Mycobacterium tuberculosis Type VII Secreted Effector EsxH Targets Host ESCRT to Impair Trafficking. Mehra A, Zahra A, Thompson V, Sirisaengtaksin N, Wells A, et al. (2013) PLoS Pathog 9(10): e1003734. doi:10.1371/journal.ppat.1003734 PMID:24204276
- Cellular communication via nanoparticle-transporting biovesicles. Ferrati S, McConnell KI, Mack AC, Sirisaengtaksin N, Diaz R, Bean AJ, Ferrari M, Serda RE Nanomedicine (Lond). 2013 Jun 3. PMID:23731456
- UBE4B levels are correlated with clinical outcomes in neuroblastoma patients and with altered neuroblastoma cell proliferation and sensitivity to epidermal growth factor receptor inhibitors. Zage, P. E., Sirisaengtaksin, Natalie, Liu, Y., Gireud, Monica, Brown, Brandon S., Palla, S., Richards, K. N., Hughes, D. P. M. and Bean, A. J., Cancer. 2013 Feb 15;119(4):915-23. PMID:22990745
- 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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