Autopsy; Computer-Assisted Instruction; Medical Informatics; Pathology; Spectrin; Telepathology
Central to the integrated function of multicellular organisms is cell contact mediated signaling and the spatial organizations of specialized membrane-surface domains. While many factors contribute, recent evidence indicates that the spectrin based membrane skeleton plays a pivotal role in these processes. Current research in the laboratory is aimed at understanding three aspects of the spectrin membrane skeleton in erythrocytes, epithelial cells, and neurons: 1) The factors that mediate its polarized assembly with specific surface membrane receptor domains; 2) the nature of the proteins that interact with spectrin and their role in signal transduction, cell differentiation, vesicle trafficking, and topographic membrane assembly; and 3) the molecular basis of diseases that involve spectrin or any of its associated proteins, including contributions of the cortical cytoskeleton to the phenotypic alterations of malignant cells and the molecular pathology of acquired and inherited disorders involving this structure. Our studies on the erythrocyte focus on a molecular understanding of how specific proteins that cause human disease.
Specialized Terms: Hemolytic Disease; Degenerative Brain Disease; spectrin; Autopsy Pathology; Renal Pathology; Medical Informatics; Computer Aided Instruction (CAI); Telepathology
Extensive Research Description
Our research focuses on understanding the structure and function of the spectrin-ankyrin-actin cytoskeleton and the mechanisms by which it mediates membrane receptor and adhesion-complex organization; signal transduction; and vesicle trafficking from the ER to the plasma membrane. Our recent studies implicate a major and unexpected role for the spectrin skeleton in the pathways of vesicle trafficking and membrane assembly. In parallel studies we are seeking to understand the molecular basis of diseases arising from aberrant cytoskeletal function. Studies are carried out both in vitro utilizing functional and biophysical assays; in cell culture using genetically modified systems; and in transgenic animals. Areas of special interest include organization of the plasma membrane in erythrocytes; vesicle trafficking and the establishment of polarity in epithelial cells; and the control of receptor organization at the synapse.
Sequential degradation of alphaII and betaII spectrin by calpain in glutamate or maitotoxin-stimulated cells.
Glantz, S.B., Cianci, C.D., Iyer, R., Pradhan, D., Wang, K.K., and Morrow, J.S. (2007). Sequential degradation of alphaII and betaII spectrin by calpain in glutamate or maitotoxin-stimulated cells. Biochem. 46(2):502-13.
Structure of the calmodulin alphaII-spectrin complex provides insight into the regulation of cell plasticity.
Simonovic, M., Zhang, Z., Cianci, C.D., Steitz, T.A., and Morrow, J,S. (2006). Structure of the calmodulin alphaII-spectrin complex provides insight into the regulation of cell plasticity. J. Biol. Chem. 281(45):34333-40.
TGFbeta induces caspase 3 independent cleavage of alpha II spectrin (alpha-fodrin) coincident with apoptosis.
Brown, T. L., Patil, S., Cianci, C. D., Morrow, J. S. and Howe, P. H. 1999. TGFbeta induces caspase 3 independent cleavage of alpha II spectrin (alpha-fodrin) coincident with apoptosis. J. Biol. Chem. in Pathology
Exclusion of the stomatin, a-adducin and b-adducin loci in a large kindred with dehydrated hereditary stomatocytosis.
Innes, D. S., Sinard, J. H., Gilligan, D. M., Snyder, L. M., Gallagher, P. G. and Morrow, J. S. 1998. Exclusion of the stomatin, a-adducin and b-adducin loci in a large kindred with dehydrated hereditary stomatocytosis. Am. J. Hematology 60:72-4.
Utilization of an 86 bp exon generates a novel adducin isoform (b4) lacking the MARCKS homology domain.
Sinard, J. H., Stewart, G. W., Argent, A. C., Stabach, P. R., Gilligan, D. M. and Morrow, J. S. 1998. Utilization of an 86 bp exon generates a novel adducin isoform (b4) lacking the MARCKS homology domain. Biochim Biophys Acta 1396:57-66.
Simultaneous degradation of aII and bII spectrin by caspase 3 (CPP32) in apoptotic cells.
Wang, K. K. W., Posmantur, R., Nath, R., McGinnis, K., Whitton, M., Talanian, R. V., Glantz, S. B. and Morrow, J. S. 1998. Simultaneous degradation of aII and bII spectrin by caspase 3 (CPP32) in apoptotic cells. J. Biol. Chem 273:22490-22497.
- Zhang, Z., Devarajan, P., Dorfman, A. L. and Morrow, J. S. 1998. Structure of the Ankyrin Binding Domain of a-Na,K-ATPase. J. Biol. Chem 273:18681-18684.
A widely expressed betaIII spectrin associated with Golgi and cytoplasmic vesicles.
Stankewich, M. C., Tse, W. T., Peters, L. L., Ch’ng, Y., John, K. M., Stabach, P. R., Devarajan, P., Morrow, J. S. and Lux, S. E. 1998. A widely expressed betaIII spectrin associated with Golgi and cytoplasmic vesicles. Proc. Natl. Acad. Sci (USA) 95:14158-14163.
Full List of PubMed Publications
- Helou E, Grant M, Landry M, Wu X, Morrow JS, Malinis MF: Fatal case of cutaneous sparing, oro-laryngeal zoster in a renal transplant recipient. Transpl Infect Dis. 2017 Apr 12; 2017 Apr 12. PMID: 28401625
- Kim JH, Kwon SJ, Stankewich MC, Huh GY, Glantz SB, Morrow JS: Reactive protoplasmic and fibrous astrocytes contain high levels of calpain-cleaved alpha 2 spectrin. Exp Mol Pathol. 2016 Feb; 2015 Nov 10. PMID: 26551084
- Stankewich MC, Moeckel GW, Ji L, Ardito T, Morrow JS: Isoforms of Spectrin and Ankyrin Reflect the Functional Topography of the Mouse Kidney. PLoS One. 2016; 2016 Jan 4. PMID: 26727517
- Vyas M, Zhang X, Morrow JS, Jain D, Salem RR, West AB: Focal hepatic glycogenosis associated with metastatic insulinoma presenting as mass lesions. Pathol Res Pract. 2016 Jan; 2015 Nov 26. PMID: 26627264
- Stankewich MC, Cianci CD, Stabach PR, Ji L, Nath A, Morrow JS: Cell organization, growth, and neural and cardiac development require αII-spectrin. J Cell Sci. 2011 Dec 1; 2011 Dec 8. PMID: 22159418
- Stankewich MC, Gwynn B, Ardito T, Ji L, Kim J, Robledo RF, Lux SE, Peters LL, Morrow JS: Targeted deletion of betaIII spectrin impairs synaptogenesis and generates ataxic and seizure phenotypes. Proc Natl Acad Sci U S A. 2010 Mar 30; 2010 Mar 15. PMID: 20231455
- Stabach PR, Simonović I, Ranieri MA, Aboodi MS, Steitz TA, Simonović M, Morrow JS: The structure of the ankyrin-binding site of beta-spectrin reveals how tandem spectrin-repeats generate unique ligand-binding properties. Blood. 2009 May 28; 2009 Jan 23. PMID: 19168783
- Stabach PR, Devarajan P, Stankewich MC, Bannykh S, Morrow JS: Ankyrin facilitates intracellular trafficking of alpha1-Na+-K+-ATPase in polarized cells. Am J Physiol Cell Physiol. 2008 Nov; 2008 Sep 3. PMID: 18768923
- Sangerman J, Maksimova Y, Edelman EJ, Morrow JS, Forget BG, Gallagher PG: Ankyrin-linked hereditary spherocytosis in an African-American kindred. Am J Hematol. 2008 Oct. PMID: 18704959
- Glantz SB, Cianci CD, Iyer R, Pradhan D, Wang KK, Morrow JS: Sequential degradation of alphaII and betaII spectrin by calpain in glutamate or maitotoxin-stimulated cells. Biochemistry. 2007 Jan 16. PMID: 17209560
- Simonovic M, Zhang Z, Cianci CD, Steitz TA, Morrow JS: Structure of the calmodulin alphaII-spectrin complex provides insight into the regulation of cell plasticity. J Biol Chem. 2006 Nov 10; 2006 Aug 31. PMID: 16945920
- Stankewich MC, Stabach PR, Morrow JS: Human Sec31B: a family of new mammalian orthologues of yeast Sec31p that associate with the COPII coat. J Cell Sci. 2006 Mar 1. PMID: 16495487
- Coleman DL, Kazdin AE, Miller LA, Morrow JS, Udelsman R: Guidelines for interactions between clinical faculty and the pharmaceutical industry: one medical school's approach. Acad Med. 2006 Feb. PMID: 16436576
- Pradhan D, Tseng K, Cianci CD, Morrow JS: Antibodies to betaISigma2 spectrin identify in-homogeneities in the erythrocyte membrane skeleton. Blood Cells Mol Dis. 2004 May-Jun. PMID: 15121100
- Gallagher PG, Zhang Z, Morrow JS, Forget BG: Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in the alpha beta spectrin self-association binding site. Lab Invest. 2004 Feb. PMID: 14661034
- Nedrelow JH, Cianci CD, Morrow JS: c-Src binds alpha II spectrin's Src homology 3 (SH3) domain and blocks calpain susceptibility by phosphorylating Tyr1176. J Biol Chem. 2003 Feb 28; 2002 Nov 20. PMID: 12446661
- Curristin SM, Cao A, Stewart WB, Zhang H, Madri JA, Morrow JS, Ment LR: Disrupted synaptic development in the hypoxic newborn brain. Proc Natl Acad Sci U S A. 2002 Nov 26; 2002 Nov 15. PMID: 12438650
- Pradhan D, Morrow J: The spectrin-ankyrin skeleton controls CD45 surface display and interleukin-2 production. Immunity. 2002 Sep. PMID: 12354383
- Schwartz MF, Duong JK, Sun Z, Morrow JS, Pradhan D, Stern DF: Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint. Mol Cell. 2002 May. PMID: 12049741