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Frederick Schachat

Associate Professor Emeritus of Cell Biology
Cell Biology
Duke Box 3011, Durham, NC 27710
466 Sands Bldg, Durham, NC 27710

Overview


We are working in three areas. The first focuses on the mechanisms that coordinate contractile protein expression in striated muscle. A variety of approaches, including comparative genomics, cDNA analysis, PCR, and genetic/biochemical analyses of expression in transgenic mice and C. elegans mutants are being used to define the how the expression of different thin filament proteins is coordinated and how the accumulation of thick and thin filament proteins is regulated. As models, we study the troponin-tropomyosin thin filament calcium regulatory complex of mammalian skeletal muscle and uncoordinated mutants of the nematode C. elegans whose phenotypes are consistent with disproportionate synthesis of thick and thin filament proteins.

The second concerns the biomoleuclar interactions involved in the cooperative activation of thin filaments in skeletal muscle contraction. These studies involve the analysis of Ca2+ and rigor crossbridge activation of skeletal muscle fibers in the presence of inhibitory peptides and following the substitution of calmodulin[troponin C] chimeras for troponin C, the Ca2+-binding subunit of the thin filament regulatory complex.

The third centers on the novel proteins and physiological systems responsible for the superfast contractile properties of extraocular muscle. These include extraocular myosin, whose gene we have cloned and mapped, a rare alternative splice variant of troponin T, and selective amplification of the Ca2+-reuptake system.

Overall, we have characterized the troponin T (TnT) and tropomyosin (Tm) species expressed in fast skeletal muscles and identified three programs of TnT-Tm expression in adult and neonatal muscle. Complementing physiological studies show that these different TnT-Tm programs control a muscle fiber's responsiveness to calcium. Strong evidence that posttranscriptional controls are critical to the coordinate expression of myofibrillar proteins has been found; and phylogenetic footprinting provides evidence for hierarchical control of the extraocular muscle specific myosin.

Current Appointments & Affiliations


Associate Professor Emeritus of Cell Biology · 2012 - Present Cell Biology, Basic Science Departments

Recent Publications


The troponin I: inhibitory peptide uncouples force generation and the cooperativity of contractile activation in mammalian skeletal muscle.

Journal Article J Muscle Res Cell Motil · May 2013 Hodges and his colleagues identified a 12 amino acid fragment of troponin I (TnI-ip) that inhibits Ca(2+)-activated force and reduces the effectiveness Ca(2+) as an activator. To understand the role of troponin C (TnC) in the extended cooperative interacti ... Full text Link to item Cite

The superfast extraocular myosin (MYH13) is localized to the innervation zone in both the global and orbital layers of rabbit extraocular muscle.

Journal Article J Exp Biol · October 2002 Featured Publication Extraocular muscles (EOMs) are the most molecularly heterogeneous and physiologically diverse mammalian striated muscles. They express the entire array of striated muscle myosins, including a specialized myosin heavy chain MYH13, which is restricted to ext ... Full text Link to item Cite

Phylogenetic implications of the superfast myosin in extraocular muscles.

Journal Article J Exp Biol · August 2002 Featured Publication Extraocular muscle exhibits higher-velocity and lower-tension contractions than other vertebrate striated muscles. These distinctive physiological properties are associated with the expression of a novel extraocular myosin heavy chain (MYH). Encoded by the ... Full text Link to item Cite
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Recent Grants


Novel Features of Extraocular Myosin Regulation

ResearchPrincipal Investigator · Awarded by National Institutes of Health · 1996 - 2006

Adductor Muscle Function and Fiber Type in Macaca and Papio

ResearchCo-Principal Investigator · Awarded by National Science Foundation · 2001 - 2006

Extraocular Muscle Plasticity And Visual Maturation

ResearchPrincipal Investigator · Awarded by National Institutes of Health · 1996 - 2001

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Education, Training & Certifications


Stanford University · 1975 Ph.D.