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.
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