Extensive Research Description
A major player of the neuronal cortical cytoskeleton is spectrin, a large and abundant scaffolding protein. The spectrin gene family is comprised of seven genes encoding two alpha and five beta subunits. To add to the complexity, many pre-mRNA splice variants have been identified. The ascribed function for spectrin is stabilizing membranes and organizing protein and lipid micro domains on both the plasma membrane and intracellular organelles. Not only is spectrin important in maintaining membrane micro domains, but also is likely involved in their targeting and transport. Salient characteristics of the spectrin gene family include: 1) a diverse neuronal compartmentalization, 2) Ca2+ /calmodulin mediated regulation, 3) calpain/caspase mediated proteolysis, and 4) tyrosine phosphorylation and ubiquination. My interest is to better elucidate the roles for such sub cellular compartmentalization and posttranslational modifications of the spectrin cytoskeleton and how spectrin affects receptor targeting, trafficking (exocytosis and endocytosis) and stabilization at pre/postsynaptic membranes.
- Ho TS, Zollinger DR, Chang KJ, Xu M, Cooper EC, Stankewich MC, Bennett V, Rasband MN. A hierarchy of ankyrin-spectrin complexes clusters sodium channels at nodes of Ranvier, Nature Neuroscience, Nov. 2014.
- Li J, Kil C, Considine K, Smarkucki B, Stankewich MC, Balgley B, Vortmeyer AO. Intrinsic indicators for specimen degradation. Lab Invest. 2013 Feb;93(2):242-53.
- Galiano MR, Jha S, Ho TS, Zhang C, Ogawa Y, Chang KJ, Stankewich MC, Mohler PJ, Rasband MN. A Distal Axonal Cytoskeleton Forms an Intra-Axonal Boundary that Controls Axon Initial Segment Assembly. Cell. 2012 May 25;149(5):1125-39.
- Stankewich M.C., Cianci C.D., Stabach P.R., Ji L, Nath A., Morrow, J.S. Cell organization, growth, and neural and cardiac development require aII-spectrin. . J. Cell. Sci. Dec. 1, 2011
- Susuki K, Raphael A.R. , Ogawa Y , Stankewich M.C., Peles E, Talbot W , Rasband MN Schwann cell spectrins modulate peripheral nerve myelination . PNAS April 25 2011.
- M. C. Stankewich, B Gywnn, T. Ardito, L. Ji, J Kim, R Robledo, . S. Lux, L. Peters, and J. S. Morrow. Targeted Deletion of ßIII Spectrin Impairs Synaptogenesis and Generates Ataxic and Seizure Phenotypes. PNAS March 15 2010.
- Riordan M, Sreedharan R, Wang S, Thulin G, Mann A, Stankewich M.C, Van Why S, Kashgarian M, Siegel NJ. HSP70 binding modulates detachment of Na-K-ATPase following energy deprivation in renal epithelial cells. Am J Physiol Renal Physiol. 2005 Jun288(6):F1236-42. 2005 Feb 8.
- A. Siddhanta, A. Radulescu, M.C. Stankewich, J.S. Morrow and D.Shields. Fragmentation of the Golgi Apparatus: A role for bIII spectrin and synthesis of phosphatidylinositol (4,5) bisphosphate. J. Biol Chem.2002.
- A.G. Vicencio, O. Eickelberg, M.C. Stankewich, M. Kashgarian, G.G Haddad. Regulation of TGF-b ligand and receptor expression in neonatal rat lungs exposed to chronic hypoxia. J. App. Physiol. 93:1123-1130 May 3 2002.
- E.A. Holleran, L.A. Ligon, M. Tokito, M.C. Stankewich, J.S. Morrow, and E.L.F. Holzbaur. bIII spectrin binds to the Arp1 subunit of dynactin. J. Biol. Chem. 276: 36598-36605 Sept. 28 2001.
- V. Muresan, M.C. Stankewich, W. Steffen, J.S. Morrow, E.L.F. Holzbaur, and B. J. Schnapp. Dynactin-Dependent, Dynein-Driven Vesicle Transport in the Absence of Membrane Proteins: A Role for Spectrin and Acidic Phospholipids. Molec. Cell 7 (1) 173-183 Jan. 19 2001.
- M.C. Stankewich, W.T. Tse, L.L. Peters, Y. ChÌng, K.M. Johns, P.R. Stabach, P. Deverajan, J.S. Morrow, and S.E. Lux. A widely expressed b spectrin associated with Golgi and cytoplasmic vesicles. P. Natl. Acad. Sci. USA 95: (24) 14158-14163 Nov. 24 1998.
- K.M. McCartney, I.B. Skare, M.C. Stankewich, R.D. Lynch, and E.E. Schneeberger. Occludin is a functional component of the tight junction. J. Cell. Sci. 109:2287-2298 Part 9 Sep. 1996.
- M.C. Stankewich, S.A. Francis, Q. Vu, E.E. Schneeberger, and R.D. Lynch. Alterations in cell cholesterol content modulate calcium-induced tight junction assembly by MDCK cells. Lipids 31: (8) 817-828 Aug. 1996.