Regulation of the centriole life cycle by MDM1
Abstract/Contents
- Abstract
- Centrosomes are composed of microtubule based structures called centrioles surrounded by a proteinaceous pericentriolar material. They serve as the primary microtubule organizing center in mammalian cells and also nucleate cilia formation. Mutations in centrosome and cilium protein coding genes are implicated in ciliopathy-related diseases and cancer. Thus, understanding functions of these proteins can aid understanding the development of these diseases. Here we study Mdm1, which we previously identified as being transcriptionally upregulated in mouse tracheal epithelial cells (MTECs). We show that MDM1 is a centriole protein with microtubule binding and stabilizing properties that localizes to newly replicated procentrioles beginning in mitosis, coincident with the end of centriole duplication. Depletion and overexpression of MDM1 results in phenotypes consistent with the protein acting as a negative regulator of centriole duplication. We also examine the role of MDM1 in MTECs, showing that it does not appear to be deuterosome-associated, but does localize to centrioles upon their formation. We further show that MDM1 disperses from centrioles upon ciliation in mature multiciliated cells. MDM1 depletion in MTECs did not block entry into the multiciliated cell fate program, but did cause a ciliation defect, suggesting MDM1 depletion may cause a delay in the development pathway of these cells.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Van de Mark, Daniel Patrick |
|---|---|
| Associated with | Stanford University, Department of Biology. |
| Primary advisor | Stearns, Tim |
| Thesis advisor | Stearns, Tim |
| Thesis advisor | Cyert, Martha S, 1958- |
| Thesis advisor | Nelson, W. J. (W. James) |
| Thesis advisor | Rohatgi, Rajat |
| Advisor | Cyert, Martha S, 1958- |
| Advisor | Nelson, W. J. (W. James) |
| Advisor | Rohatgi, Rajat |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Daniel Patrick Van de Mark. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Daniel Patrick Van de Mark
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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