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Phosphorylation controls CLIMP-63-mediated anchoring of the endoplasmic reticulum to microtubules.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 2005 Apr; Vol. 16 (4), pp. 1928-37. Date of Electronic Publication: 2005 Feb 09. - Publication Year :
- 2005
-
Abstract
- The microtubule-binding 63-kDa cytoskeleton-linking membrane protein (CLIMP-63) is an integral membrane protein that links the endoplasmic reticulum (ER) to microtubules. Here, we tested whether this interaction is regulated by phosphorylation. Metabolic labeling with (32)P showed that CLIMP-63 is a phosphoprotein with increased phosphorylation during mitosis. CLIMP-63 of mitotic cells is unable to bind to microtubules in vitro. Mitotic phosphorylation can be prevented by mutation of serines 3, 17, and 19 in the cytoplasmic domain of CLIMP-63. When these residues are mutated to glutamic acid, and hence mimic mitotic phosphorylation, CLIMP-63 does no longer bind to microtubules in vitro. Overexpression of the phospho-mimicking mitotic form of CLIMP-63 in interphase cells leads to a collapse of the ER around the nucleus, leaving the microtubular network intact. The results suggest that CLIMP-63-mediated stable anchoring of the ER to microtubules is required to maintain the spatial distribution of the ER during interphase and that this interaction is abolished by phosphorylation of CLIMP-63 during mitosis.
- Subjects :
- Amino Acid Sequence
Animals
Cell Line
Chlorocebus aethiops
Humans
Membrane Proteins chemistry
Membrane Proteins genetics
Mitosis
Molecular Sequence Data
Mutation genetics
Phosphorylation
Phosphoserine metabolism
Endoplasmic Reticulum metabolism
Membrane Proteins metabolism
Microtubules metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1059-1524
- Volume :
- 16
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 15703217
- Full Text :
- https://doi.org/10.1091/mbc.e04-07-0554