This is an application for a FIRST award. The goal of this project is to understand the synthesis, assembly and degradation of oligomeric membrane protein channels. Most experiments will be conducted on the gap junction protein, connexin, although other membrane protein channels will also be studied. The investigator will use cell-free and culture cell expression systems, as well as various mammalian tissues, toward the following specific aims: (1) to examine the subunit composition and stoichiometry of oligomeric membrane channels; (2) to characterize the mechanisms that underlie the assembly and subunit composition of membrane channels, and (3) to determine the specific factors and mechanisms in the synthesis and maturation of oligomeric membrane channels in intact cell systems.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Shapiro, Bert I
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Scripps Research Institute
La Jolla
United States
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Kells-Andrews, Rachael M; Margraf, Rachel A; Fisher, Charles G et al. (2018) Connexin-43 K63-polyubiquitylation on lysines 264 and 303 regulates gap junction internalization. J Cell Sci 131:
Thévenin, Anastasia F; Margraf, Rachel A; Fisher, Charles G et al. (2017) Phosphorylation regulates connexin43/ZO-1 binding and release, an important step in gap junction turnover. Mol Biol Cell 28:3595-3608
Falk, Matthias M; Bell, Cheryl L; Kells Andrews, Rachael M et al. (2016) Molecular mechanisms regulating formation, trafficking and processing of annular gap junctions. BMC Cell Biol 17 Suppl 1:22
Nimlamool, Wutigri; Andrews, Rachael M Kells; Falk, Matthias M (2015) Connexin43 phosphorylation by PKC and MAPK signals VEGF-mediated gap junction internalization. Mol Biol Cell 26:2755-68
Kowal, Tia J; Falk, Matthias M (2015) Primary cilia found on HeLa and other cancer cells. Cell Biol Int 39:1341-7
Fong, John T; Nimlamool, Wutigri; Falk, Matthias M (2014) EGF induces efficient Cx43 gap junction endocytosis in mouse embryonic stem cell colonies via phosphorylation of Ser262, Ser279/282, and Ser368. FEBS Lett 588:836-44
Falk, Matthias M; Kells, Rachael M; Berthoud, Viviana M (2014) Degradation of connexins and gap junctions. FEBS Lett 588:1221-9
Wang, Shaojie; Kowal, Tia J; Marei, Mona K et al. (2013) Nanoporosity significantly enhances the biological performance of engineered glass tissue scaffolds. Tissue Eng Part A 19:1632-40
Thevenin, Anastasia F; Kowal, Tia J; Fong, John T et al. (2013) Proteins and mechanisms regulating gap-junction assembly, internalization, and degradation. Physiology (Bethesda) 28:93-116
Fong, John T; Kells, Rachael M; Falk, Matthias M (2013) Two tyrosine-based sorting signals in the Cx43 C-terminus cooperate to mediate gap junction endocytosis. Mol Biol Cell 24:2834-48

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