Microtubule stability mediated by new mammalian STOP family members
Abstract/Contents
- Abstract
- Stable Tubule Only Polypeptides or STOP proteins are a class of microtubule-associated proteins that are unique in that they have been shown to protect microtubules from depolymerization under destabilizing conditions. To date, MAP6 and the related protein MAP6 domain containing 1 (MAP6D1) are the only known mammalian STOP related proteins. However, through a recent screen identifying genes upregulated during ciliogenesis in multiciliated tracheal cells, we have identified two new uncharacterized mammalian MAP6 related proteins, FAM154A and FAM154B. Though MAP6 has not been previously shown to localize to the primary cilium and centrosome, we sought to assess the ability of these new proteins to stabilize microtubules and their potential function at the cilium and centrosome. Proteins related to FAM154A and FAM154B are found in all vertebrates and most organisms containing cilia and centrosomes including drosophila and chlamydomonas. A C. elegans homolog of the protein has been localized to neuronal cilia and mammalian FAM154B, much like MAP6 is expressed in mammalian cortical neurons. Overexpressed FAM154A and FAM154B localize to the centrosome and the primary cilium and overexpressed FAM154A protein and deletion variants stabilize microtubules against cold treatment in RPE1 cells. Endogenous FAM154A and FAM154B localize to centrosomal structures and cilia respectively in multi-ciliated cells. Similar to MAP6, FAM154A and Fam154B also contain repeated motifs in their amino acid sequences, however their protein level similarity to MAP6 is very limited. We have shown that FAM154A is a bona-fide microtubule associated protein via biochemical assays and can interact directly with microtubules and with calcium calmodulin which may modulate its microtubule binding affinity, similar to MAP6. Ongoing work to resolve the molecular structure of these MAP6 related proteins will illuminate their exact mechanism of microtubule stabilization.
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 | Onyeneho, Irene Adaugo |
|---|---|
| Associated with | Stanford University, Department of Molecular and Cellular Physiology. |
| Primary advisor | Stearns, Tim |
| Thesis advisor | Stearns, Tim |
| Thesis advisor | Downing, Kenneth (Kenneth H.) |
| Thesis advisor | Yang, Yanmin, Ph. D |
| Advisor | Downing, Kenneth (Kenneth H.) |
| Advisor | Yang, Yanmin, Ph. D |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Irene Adaugo Onyeneho. |
|---|---|
| Note | Submitted to the Department of Molecular and Cellular Physiology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Irene Adaugo Onyeneho
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