G. Vann Bennett (Primary)
Mechanisms for micron-scale organization of vertebrate plasma membranes.
214A Nanaline H Duke, Durham, NC 27710 Box 3711 Med Ctr, Durham, NC 27710
Functional organization of vertebrate plasma membranes: Molecules to Physiology
Plasma membrane proteins such as ion transporters, cell adhesion molecules, and signaling receptors all must segregate to specific cellular compartments to perform their physiological roles. Our laboratory has discovered an adaptable mechanism based on ankyrins and their spectrin partners that is responsible for coordinating functionally related membrane-spanning proteins within micron-scale domains in diverse vertebrate plasma membranes including excitable membranes in the nervous system and heart. Ankyrins recognize cytoplasmic domains of membrane transporters and cell adhesion proteins (15 protein families identified so far) through independently evolved interactions of intrinsically disordered sequences with a highly conserved peptide-binding groove formed by the ANK repeat solenoid. Ankyrins are coupled to spectrins, which are elongated organelle-sized proteins that form mechanically resilient arrays through crosslinking by specialized actin filaments. In addition, giant vertebrate ankyrins with specialized roles in axons acquired new coding sequences by exon shuffling early in vertebrate evolution.
Our current research focuses on three general areas/questions:
1. The role of the axon initial segment in neuronal plasticity.
2. Ankyrin-B metabolic syndrome, which combines impaired insulin secretion with age-dependent adiposity and insulin resistance.
3. Mechanisms for directed organelle transport.
4. The role ANK2 (the gene encoding ankyrin-B) in neurodevelopment and how ANK2 mutation leads to autism spectrum disorder.
- Fellow. American Association for the Advancement of Science. 2013
- Fellow. Association of American Physicians. 2013
- Member. National Academy of Sciences of the USA. 2010
- Fellow. American Academy of Arts and Sciences. 2009
- Merit Award. NIH. 1990
- Investigator. Howard Hughes Medical Institute. 1987
- Member. American Society of Clinical Investigation. 1987
- Outstanding Young Scientist of the year in Maryland, 1982
M.D., Johns Hopkins University 1976
Ph.D., Johns Hopkins University 1975
- Jenkins, PM, He, M, and Bennett, V (2015) Dynamic spectrin/ankyrin microdomains promote lateral membrane assembly by opposing endocytosis. Science Advances Sept 11; 1(8):e1500301
- Lorenzo DN, Healy JA, Hostettler J, Davis J, Yang J, Wang C, Hohmeier HE, Zhang M, Bennett V. (2015) Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic β cell insufficiency. J Clin Invest. 125:3087-102
- Bennett, V, and Walder, K. "Evolution in action: giant ankyrins awake." Developmental cell 33, no. 1 (April 2015): 1-2. Full Text
- Jenkins, PM, Kim, N, Jones, SL, Tseng, WC, Svitkina, TM, Yin, HH, and Bennett, V. "Giant ankyrin-G: a critical innovation in vertebrate evolution of fast and integrated neuronal signaling." Proceedings of the National Academy of Sciences of the United States of America 112, no. 4 (January 2015): 957-964. Full Text
- Zhong G, He J, Zhou R, Lorenzo D, Babcock HP, Bennett V, Zhuang X. (2014) Developmental mechanism of the periodic membrane skeleton in axons.Elife. Dec 23;3. doi: 10.7554/eLife.04581.
- Lorenzo, DN, Badea, A, Davis, J, Hostettler, J, He, J, Zhong, G, Zhuang, X, and Bennett, V. "A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport." The Journal of cell biology 207, no. 6 (December 2014): 735-752. Full Text
- Tseng, WC, Jenkins, PM, Tanaka, M, Mooney, R, and Bennett, V. "Giant ankyrin-G stabilizes somatodendritic GABAergic synapses through opposing endocytosis of GABAA receptors." Proceedings of the National Academy of Sciences of the United States of America 112, no. 4 (January 2015): 1214-1219. Full Text
- Wang, C, Wei, Z, Chen, K, Ye, F, Yu, C, Bennett, V, and Zhang, M. "Structural basis of diverse membrane target recognitions by ankyrins." eLife 3 (January 2014). Full Text
- He, M, Abdi, KM, and Bennett, V. "Ankyrin-G palmitoylation and βII-spectrin binding to phosphoinositide lipids drive lateral membrane assembly." The Journal of cell biology 206, no. 2 (July 2014): 273-288. Full Text