About
Titles
C. N. H. Long Professor of Cellular And Molecular Physiology and Professor of Cell Biology
Chair, Cellular and Molecular PhysiologyBiography
Michael J. Caplan received his bachelors degree from Harvard University and his M.D. and Ph.D. degrees from Yale University in 1987. He joined Yale's Department of Cellular and Molecular Physiology as a faculty member in 1988, and is currently the C.N.H. Long Professor of Cellular and Molecular Physiology and Cell Biology.
He has received fellowships from the Helen Hay Whitney Foundation, the David and Lucille Packard Foundation for Science and Engineering, and a National Young Investigator Award from the National Science Foundation. He has also received the Young Investigator Awards from the American Physiological Society and the American Society of Nephrologists.
His work focuses on understanding the ways in which kidney cells organize and maintain their unique structures. His laboratory also studies the mechanisms responsible for Autosomal Dominant Polycystic Kidney Disease, and is working to identify targets for new therapies.
Appointments
Cellular & Molecular Physiology
ChairDualCellular & Molecular Physiology
ProfessorPrimaryCell Biology
ProfessorSecondary
Other Departments & Organizations
- Caplan Lab
- Cell Biology
- Cellular & Molecular Physiology
- Diabetes Research Center
- Graduate Program in Cellular and Molecular Physiology
- Membrane Traffic
- Molecular Cell Biology, Genetics and Development
- Molecular Medicine, Pharmacology, and Physiology
- Program in Translational Biomedicine (PTB)
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Ventures
Education & Training
- PhD
- Yale University (1987)
- MD
- Yale University (1987)
- AB
- Harvard University, Biology (1980)
Research
Overview
Work in the Caplan laboratory is focused on understanding how membrane proteins are sorted to the appropriate cell surface domains of polarized epithelial cells. One of the proteins whose trafficking we study is the Na,K-ATPase, or sodium pump, which generates the ion gradients responsible for most fluid and electrolyte transport processes in the kidney. The Na,K-ATPase must be restricted to the basolateral surfaces of renal tubule epithelial cells. Much remains to be learned about the partner proteins and trafficking pathways that determine the sodium pump’s subcellular distribution and modulate its activity. We have adapted a novel labeling methodology to investigate the attributes of temporally defined cohorts of Na,K-ATPase.
We can observe directly the trafficking itinerary pursued by newly synthesized Na,K-ATPase and isolate newly synthesized Na,K-ATPase in association with its collections of partner proteins. We find that the basolateral delivery of newly synthesized Na,K-ATPase occurs via a pathway distinct from that pursued by other basolateral membrane proteins. We have also detected interactions between the Na,K-ATPase a-subunit and a collection of novel partner proteins that may govern the pump’s trafficking properties. Thus, we have developed tools that permit us to evaluate the trafficking pathways and partner proteins that govern the post-synthetic sorting and regulation of the epithelial Na,K-ATPase.
We also study a common genetic disease that dramatically alters the structure and function of polarized epithelial cells. In Autosomal Dominant Polycystic Kidney Disease (ADPKD) the normal architecture of the kidney tubules is replaced by large fluid filled cysts, which can ultimately result in renal failure. ADPKD is caused by mutations in the PKD1 or PKD2 genes, which encode the polycystin-1 and polycystin-2 proteins, respectively. Both of these proteins are targeted to cilia in polarized epithelial cells. We have found that polycystin-1 undergoes such a proteolytic cleavage that releases its C-terminal tail (CTT), which enters the nucleus and initiates signaling processes. The cleavage occurs in vivo in association with alterations in mechanical stimuli that may be communicated by signaling through the cilium. The C-terminal tail fragment of polycystin-1 participates in a complex with ß-catenin and acts to profoundly inhibit canonical ß-catenin-dependent Wnt signaling. The polycystin-1 C-terminal tail fragment also appears to modulate gene expression, and may induce expression of cilia-related proteins in renal epithelial cells.
We find that all of the signal transduction machinery found in the cilia of olfactory epithelial cells is present in renal epithelial cells. Our data suggest that olfactory receptors and proteins involved in olfactory signal transduction may play a role in regulating renal flow or transport in response to chemosensory cues.
Medical Subject Headings (MeSH)
Academic Achievements and Community Involvement
Links & Media
News
- May 02, 2024
AAAS Elects 3 From Yale School of Medicine
- April 30, 2024
Caplan Is Honored by the PKD Foundation
- March 20, 2024
The power of collaboration
- October 24, 2023
Yale Contributions Shape ASN Kidney Week 2023
Get In Touch
Contacts
Cellular & Molecular Physiology
PO Box 208026, 333 Cedar Street
New Haven, CT 06520-8026
United States