Section: Research

Gregory Pazour, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Program in Molecular Medicine

Other Affiliation(s):
   Interdisciplinary Graduate Program
   Program in Cell Dynamics

The role of the intraflagellar transport (IFT) proteins in eukaryotic ciliary assembly

I am working to understand the role of the intraflagellar transport (IFT) proteins in eukaryotic ciliary assembly and to understand how ciliary defects can lead to disease.

Cilia are assembled and maintained by a process called intraflagellar transport in which a large protein complex is carried along ciliary microtubules. The IFT particle is composed of ~15 polypeptides of unknown function. We recently showed that the IFT88 subunit of this complex is required for ciliary assembly in Chlamydomonas and in mice. Mice with defects in this gene have polycystic kidney disease. The reason that a ciliary defect causes polycystic kidney disease is unknown, but each of the epithelial cells lining the ducts and tubules of the kidney have a non-motile cilium extending from their apical surface. The function of the kidney cilia is not known, but cilia often are used as sensory organelles and may be playing such a role in the kidney. We are currently looking for sensory proteins that are localized to kidney cilia in order to understand the function of these structures.

In the vertebrate eye, photoreceptor proteins are organized in modified cilia called rod and cone outer segments. The outer segments develop from a primary cilium by moving membrane and opsin into the cilium. Large amounts of membrane and protein transport are required during development of the outer segment and also to replace normal turnover of outer segment proteins and membrane. The transport mechanisms are not understood, but since they occur in a cilium, IFT is likely to be involved. We have shown that several IFT proteins are localized to photoreceptor cilia and that mice defective in a gene encoding an IFT protein have rod outer segment defects. With time, the defective photoreceptor cells die in way that is similar to how photoreceptors are lost in humans with progressive retinal degeneration diseases such as retinitis pigmentosa. This work indicates that IFT is an important transport mechanism in photoreceptor cells and suggests that some humans with retinitis pigmentosa may have defects in IFT.

Office: B2-213
Phone: 508-856-8078
Fax: 508-856-5612
E-mail: Gregory.Pazour@umassmed.edu
Keywords: Genetic Systems, Cell Biology, Intracellular Trafficking

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