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Vol. 16, Issue 4, 1928-1937, April 2005

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Phosphorylation Controls CLIMP-63–mediated Anchoring of the Endoplasmic Reticulum to Microtubules

Biozentrum, University of Basel, CH-4056 Basel, Switzerland

Submitted July 6, 2004; Accepted January 24, 2005
Monitoring Editor: Jennifer Lippincott-Schwartz

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 ³²P 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.

Abbreviations used: CKII, casein kinase II; CLIMP-63, 63-kDa cytoskeleton-linking membrane protein; CLIP, cytoskeleton linking protein; ER, endoplasmic reticulum; MAP, microtubule-associated protein; MT, microtubule; pc, polyclonal antibody; PKC, protein kinase C; wt, wild-type.

^* Present address: Center for Molecular Physiology of the Brain, Georg August University, D-37073 Göttingen, Germany.

Address correspondence to: Hans-Peter Hauri (hans-peter.hauri{at}unibas.ch).

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