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Playing in traffic: novel signaling and trafficking mechanisms in the kidney
Speaker: Professor Michael Caplan (C.N.H. Long Professor and Chair of the Department of Cellular and Molecular Physiology, Yale University School of Medicine).
Date: 13th November 2012
Time: 17.30 (Followed by a reception)
Location: J. Z. Young Lecture Theatre, Medical Sciences and Anatomy Building, Gower Street.
This free lecture is part of the Yale UCL Collaborative (Biomedicine) Senior Scientist Lecture Series and the speaker is Professor Michael Caplan (C.N.H. Long Professor and Chair of the Department of Cellular and Molecular Physiology, Yale University School of Medicine).
The physiological properties of epithelial cells are determined largely by the ion transport proteins that occupy their apical and basolateral plasma membrane domains. Generation and maintenance of epithelial polarity requires cells to possess sorting machinery that discriminates among newly synthesized membrane proteins and sends them to their appropriate subcellular destinations. To follow the post-synthetic fate of newly synthesized epithelial membrane proteins, we have adapted a technique that permits direct observation of temporally-defined cohorts of proteins via the combination of fluorescence microscopy with pulse-chase labeling protocols. This technique also allows us to purify temporally-defined cohorts of proteins of interest and thus to begin to define their "temporal interactomes".
Perturbations in epithelial morphogenesis are associated with a number of human genetic diseases, the most common of which is Autosomal Dominant Polycystic Kidney Disease (ADPKD). Affecting ~1:1,000 individuals, ADPKD is associated with the replacement of renal nephrons with fluid-filled cysts that ultimately compromise renal function. Although the genes responsible for ADPKD are known, their functions remain mysterious. We find that one of the proteins encoded by an ADPKD gene undergoes a cleavage that releases a fragment that enters the nucleus and modulates transcription. We have begun to elucidate the signaling pathways involved in this process and have identified new potential therapeutic targets.
Finally, we find that the signal transduction machinery present in the cilia of olfactory neurons is also present in renal epithelial cells. Our data suggest that olfactory receptors participate in regulating renal function in response to chemosensory cues.
Admission is free and open to all either on a first-come first-served basis or places may be reserved in advance.
The lecture will be followed by a reception.