Mark M. Rasenick
Professor
Physiology and Biophysics, and Psychiatry
Director, Biomedical Neuroscience Training Program
Cytoskeletal modulation of neuronal signal transduction
Mark M. RasenickProfessorPhysiology and Biophysics, and Psychiatry Director, Biomedical Neuroscience Training Program Cytoskeletal modulation of neuronal signal transduction |
|
Most of the work in my laboratory involves the possibility that a structural protein, tubulin, conveys a dynamic response and alters the ability of a neurotransmitter to convey it's message across the synapse. It appears that tubulin forms specific complexes with certain G proteins (the intracellular harbingers of neurotransmitter messages) and activates them via the direct transfer of GTP. In this manner, a neurotransmitter which had no direct effect upon a certain G protein mediated pathway could affect that pathway by increasing (or decreasing) the activation of a G protein via tubulin. It is also possible that changes in synaptic shape or the synaptic cytoskeleton, which occur during chronic neural activity, might alter responsiveness to a neurotransmitter. Several changes in the cytoskeleton have been noticed in both the developing and the degenerating nervous system. The neurotransmitter G protein axis could be responsible for altered cytoskeletal form (and consequently, altered synaptic development) and might provide an forum whereby activity in one neuron could dictate development of the synapse. A variety of molecular techniques are being employed to elucidate this system. It is hoped that a better understanding of the interface between the cytoskeleton and G protein mediated signal transduction systems could provide a better understanding of brain and mind function and dysfunction.
Rasenick, M.M. Gs (a poem). Trends in Biochem. Sci. 17:71, 1992.
Selected Publications:
1) Popova, J.S., Garrison, J.C., Rhee, S.G. and RASENICK, M.M. Tubulin, Gq and phosphatidylinositol 4,5-bisphosphate interact to regulate phospholipase C 1 signaling. J. Biol. Chem. 272:6760-6765, 1997.
2) Roychowdhury, S. and RASENICK, M.M. G-protein bg subnits regulate microtubule assembly. J. Biol. Chem. 50:31576-31581, 1997.
3) Roychowdhury, S., Panda, D., Wilson, L. and RASENICK, M.M. G protein a subunits activate tubulin GTPase and modulate microtubule polymerization dynamics. J. Biol. Chem. 274:13485-13490, 1999.
4) Toki, S., Donati, R.J. and RASENICK, M.M. Treatment of C6 Glioma cells and rats with antidepressant drugs increases the detergent extraction of Gsa from plasma membrane. J. Neurochem. 73:1114-1120, 1999.
5) Popova, J.S. and RASENICK, M.M. Muscarinic receptor activation promotes the membrane association of tublin for the regulation of Gq-mediated phospholipase Cb1 signaling. J. Neurosci. 20:2774-2782, 2000.
6) Yan, K., Popova, J.S., Moss, A., Shah, B. and RASENICK, M.M. Tubulin stimulates adenylyl cyclase activity in C6 glioma cells by bypassing the b-adrenergic receptor: a potential mechanism of G protein activation. J. Neurochem., 76:182-190, 2001.
7) Donati, R., Thukral, C. and RASENICK, M.M. Chronic treatment of C6 glioma cells with antidepressant drugs results in a redistribution of Gsa. Mol. Pharmacol., 59(6):1-7, 2001.
8) Yu, J.Z. and RASENICK, M.M. Real-time visualization of a fluorescent Gas: Dissociation of the activated G protein from the plasma membrane. Mol. Pharmacol., 61:352-359, 2002.
9) Yu, J.Z. and RASENICK, M.M. Transient expression of fluorescent tau proteins promotes process formation in PC12 cells: Contributions of the tau C-terminus to this process. J. Neurosci. Res., 67:625-633, 2002.
10) Popova, J.S., Greene, A., Wang, J. and RASENICK, M.M. Phophatidylinositol 4,5-bisphosphate modifies tubulin participation in PLCb1 signaling. J. Neuroscience, 22:1668-1678, 2002.
11) Sarma, T., Voyno-Yasenetskaya, T., Hope, T.J. and RASENICK, M.M. Heteotrimeric G proteins associate with microtubules during differentiation. FASEB J., 17: 848-859, 2003.
12) Donati, R.J. and RASENICK, M.M. G protein signaling and the molecular basis of antidepressant action, (invited review). Life Sciences, 73:1-17, 2003.
13) Chen, N-F, Yu, J-Z, Skiba, N.P., Hamm, H.E. and RASENICK, M.M. A specific domain of Gi required for the transactivation of Gi by tubulin is implicated in the organization of cellular microtubules. J. Biol. Chem, 278: 15285-15290. 2003.
14) Popova, J.S. and RASENICK, M.M. G mediates the interplay between tubulin dimers and microtubules in the modulation of Gq signaling. J. Biol. Chem., 278, 34299-34308, 2003.
15) Popova, J.S. and RASENICK, M.M. Clathrin-mediated endocytosis of
m3 muscarinic receptors. Roles for Gbetagamma and tubulin J. Biol.Chem.,
279 30410-30418, 2004.
16) Allen, J, Yu, J-Z, Donati, R.J. and RASENICK, M.M. Beta Adrenergic Receptor Stimulation Promotes Galpha s Internalization Through Lipid Rafts: A Study in Living Cells
Mol. Pharmacol 67-1493-1504, 2005
17) Yu, J-Z and RASENICK, M.M. Tau associates with actin in differentiating PC12 cells. FASEB J.. 20: 1-10, 2006.
18) Allen J, Halvorsen R, and RASENICK MM Lipid Raft Microdomains and Neurotransmitter Signaling. NATURE Reviews Neuroscience 8:128-140, 2007.
09/21/07