The Rilp-like proteins and ciliary trafficking
- Johanna Roberta Schaub.
- Aug. 2012.
- Physical description
- online resource (viii, 111 pages) : illustrations (some color)
- Schaub, Johanna Roberta.
- Nelson, W. J. (W. James) thesis advisor.
- Oro, Anthony, 1958- thesis advisor.
- Sage, Julien. thesis advisor.
- Stearns, Tim. thesis advisor (primary).
- Stanford University. Program in Cancer Biology.
- Stanford University. Committee on Graduate Studies. degree grantor.
- Includes bibliographical references (p. 95-111). 189 refs.
- Primary cilia have critical sensory and signaling roles in development and disease. These functions rely on the proper localization of structural and signaling proteins to the cilium. Ciliary trafficking is the movement of proteins to, within, and from the cilium, processes that are regulated by several classes of proteins, for example: endo- and exocytic machinery, diffusion barriers, and motor proteins. To understand how ciliary trafficking is regulated we used gene expression data from multi-ciliated cells to identify two proteins involved in ciliary trafficking: the Rilp-like proteins Rilpl1 and Rilpl2. We took three approaches to characterizing these proteins: 1) examining localization of Rilpl1 and Rilpl2 in mammalian cells, 2) determining the phenotype of cells depleted of Rilpl1 and/or Rilpl2, and 3) identifying interaction partners. We found that Rilpl2 is up-regulated during ciliogenesis and localizes to the centrosome and primary cilium. Rilpl1 also localizes to the primary cilium and is a distal mother centriole protein with cell-cycle dependent localization. Additionally, Rilp-like proteins form dynamic tubules from the base of the cilium, which are microtubule dependent and induced by disruption of the actin network. Depletion of Rilpl1 and/or Rilpl2 from ciliated cells leads to an accumulation of signaling proteins in the ciliary membrane and disrupts epithelial cell organization in three-dimensional culture. We also determined that both Rilpl1 and Rilpl2 interact with Rab36. Taken together, our data suggest that Rilp-like proteins control ciliary protein content through the regulation of ciliary protein removal.
- Adaptor Proteins, Signal Transducing > genetics
- Cilia > metabolism
- Epithelial Cells > metabolism
- Signal Transduction
- Centrioles > metabolism
- Gene Expression Regulation
- Publication date
- Submitted to the Program in Cancer Biology and the Committee on Graduate Studies of Stanford University.
- Thesis (Ph.D.)--Stanford University, 2012.