Jakob Schmidt

M.D., University Munich, 1966; Ph.D., University of California, Riverside, 1970
Professor, Department of Biochemistry and Cell Biology

Research Interests: Regulation of acetylcholine receptor genes in muscle

Research in the laboratory focuses on the regulation of acetylcholine receptor (AChR) expression in skeletal muscle. We are especially interested in two processes: 1) how receptor genes are turned on during differentiation, i.e., when myoblasts fuse to form myofibers; and 2) how receptor genes are turned off selectively in response to the electrical activity of the plasma membrane, i.e., when the myofibers become innervated.

We have analyzed promoters of the alpha, gamma and delta subunit genes and identified a consensus sequence which comprises as its core a CANNTG motif or MyoD binding site. Our search for transcription factors that activate this cis element is guided by the assumption that helix-loop-helix (HLH) proteins, in particular the family of myogenic factors which recognize this motif, also participate in the regulation of AChR genes; additional candidate proteins have been identified by expression cloning. Using probes specific for these transcription factors we have studied their expression during development and in the denervated and denervated-stimulated muscle.

These experiments have revealed that the signaling pathway linking membrane depolarization with AChR gene transcription involves the L-type calcium channel in the plasma membrane and protein kinase C in the nucleus; they also suggest that myogenin, which is rapidly phosphorylated and inactivated by depolarization, functions in AChR gene control.

Huang, C.-F., Tong, J. and Schmidt, J. (1992) Protein kinase C couples membrane excitation to acetylcholine receptor gene inactivation in chick skeletal muscle. Neuron 9: 671-678.

Huang, C.-F., Lee, Y.-S., Schmidt, M.M. and Schmidt, J. (1994) Rapid inhibition of myogenin-driven acetylcholine receptor subunit gene transcription. EMBO J. 13: 634-640.