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Dahms, Steve A.
ccmbpa,CMB-Professor Ph.D., Michigan State University, Director Biotechnology Research and Training Program, Director Twenty Campus CSU
Membrane Molecular Biology
The research in our laboratories is directed towards the study of biological membranes, specifically the elucidation of membrane structure-function relationships and associated membrane regulatory phenomena. Of considerable importance to us are those membranes which are capable of biological energy transductions, especially membranes exhibiting phenomena driven by or involved with ATP. A major concern of our laboratories has been a probing of ATPase mechanisms, the nature of nucleotide binding sites and their cooperative interactions, conformationally-sensitive regulatory interactions, and the mapping of requisite sub-site components. Among the approaches used in studying these ATPases are protein sequencing, chemical and isotopic probes, light-activated active site and membrane surface labeling reagents, immunological probes, plasmon resonance spectroscopy, and recombinant DNA techniques.
Most of our attention is directed towards a relatively new enzyme present in muscle plasma membranes whose role is not fully understood. This extremely efficient Ca/Mg-ATPase is an ecto-ATPase and is elegantly regulated by lipid second messengers, including diacylglycerols and sphingoid bases. We are evaluating its regulation by other lipid regulators and the role of the enzyme in modulating muscle extracellular ATP-dependent reactions, including its serving as a master switch for controlling purinolig and accessibility to purinergic receptors, ecto-protein kinases, and receptors such as the insulin receptor.
Additionally, we have demonstrated by a combination of enzymatic, immunological and protein sequencing techniques that the same ecto-ATPase is unexpectedly also located in brain (synaptic) plasma membranes. We have proposed and will be pursuing the possibility that the brain ecto-ATPase may modulate the recently discovered neurotransmitter role of ATP. The Ca/ Mg-ATPase contains an 85K glycoprotein regulatory subunit that we have shown to be identical to a CA2+-dependent homophilic cellular adhesion protein, T-cadherin. We have also found structural variants of the 85K glycoprotein in both cardiac myocytes and smooth muscle, and the former appears to be an alternate post-translational glycosylation product. There is also evidence that the enzyme may be regulated by endogenous lectins that further amplify the mechanics of cellular adhesion.
Other future work will examine ATP involvement in cellular adhesion, tissue-dependent and developmentally-regulated gene expression of other ATPase subunits, enzymatic regulation, modes and positions of glycosylation, membrane sidedness and orientation, and ATPase involvement in controlling vascular responses. Intensive focus will be on the role of the enzyme in regulating the production of adenosine, a major vascular regulator.
Soto-Gil, R.W., L. Childers, W.H. Huisman, A.S. Dahms, and J.W. Zyskind. N,N'-Diacetylchitobiase of Vibrio harveyi. Meth. Enzymol. 161B:524-529 (1989).
Sabbadini, R.A. and A.S. Dahms. Biochemical properties of isolated transverse tubular membranes. J. Bioenerg. and Bio. Membr. 21:163-213 (1989).
Yazaki, P.J., S. Salvatori, R.A. Sabbadini, and A.S. Dahms. Calsequestrin, an intracellular calcium-binding protein of skeletal muscle sarcoplasmic reticulum, is homologous to aspartactin, a putative laminin-binding protein of the extracellular matrix. Biochem. Biophys. Res. Commun. 166, 2, 898-903 (1990).
Yazaki, P.J., S. Salvatori, and A.S. Dahms. Amino acid sequence of chicken calsequestrin deduced from cDNA: comparison of calsequestrin and aspartactin. Biochem. Biophys. Res. Commun. 170 1089-1095 (1990).
Kang,, J.J., B.R. Cunningham, C. Jachec-Schmidt, A.M. Priest, R.A. Sabbadini, and A.S. Dahms. Structural, enzymatic and regulatory properties of the transverse tubular Mg ATPase-its role as a receptor for diacylglycerol. Ann. N.Y. Acad. Sci. 603-530-533 (1990).
Kang, J.J., H.B. Cunningham, C. Jachec-Schmidt, A.M. Priest, A.S. Dahms, and R.A. Sabbadini. Direct effects of phorbol esters and diacylglycerols on the T-Tubule MG2+-ATPase. Arch. Biochem. Biophy. 290, 2145 (1991).
Yazaki, P.J., H.B. Cunningham, J.J. Kang, C. Jachec-Schmidt, S.A. Hunt, R.C. Domingo, R.A. Sabbadini, and A.S. Dahms. Characterization of a muscle membrane glycoprotein. Advan Experim. Med. 311, 425 (1992).
Cunningham, H.B., P.J. Yazaki, K.V. Oades, H. Bohnen, R.A. Sabbadini, and A.S. Dahms,.The skeletal muscle transverse tubular MgATPase: Identity with MgATPases of smooth muscle and brain. Arch. Biochem. Biophys. 302, 32 (1993).
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