A Ca2+-dependent Mechanism of Neuronal Survival Mediated by the Microtubule-associated Protein p600

被引：17

作者：

Belzil, Camille ^{[1
,2
,3
,4
]}

Neumayer, Gernot ^{[1
,2
,3
,4
]}

Vassilev, Alex P. ^{[5
]}

Yap, Kyoko L. ^{[6
]}

Konishi, Hiroaki ^{[7
]}

Rivest, Serge ^{[8
]}

Sanada, Kamon ^{[9
]}

Ikura, Mitsuhiko ^{[6
]}

Nakatani, Yoshihiro ^{[10
]}

Minh Dang Nguyen ^{[1
,2
,3
,4
]}

机构：

[1] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada

[2] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 4N1, Canada

[3] Univ Calgary, Dept Cell Biol & Anat, Calgary, AB T2N 4N1, Canada

[4] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada

[5] NICHD, NIH, Bethesda, MD 20892 USA

[6] Univ Toronto, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada

[7] Prefectural Univ Hiroshima, Fac Life & Environm Sci, Shobara, Hiroshima 7270023, Japan

[8] Univ Laval, Ctr Hosp Univ Laval, Ctr Rech, Quebec City, PQ G1V 0A6, Canada

[9] Univ Tokyo, Grad Sch Sci, Mol Genet Res Lab, Bunkyo Ku, Tokyo 1130033, Japan

[10] Dana Farber Canc Inst, Boston, MA 02115 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2013年 / 288卷 / 34期

基金：

加拿大健康研究院;

关键词：

ENDOPLASMIC-RETICULUM STRESS; METHYL-D-ASPARTATE; KINASE-II CLUSTERS; ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASES; CEREBRAL-ISCHEMIA; INDUCED APOPTOSIS; CNS NEURONS; CALCIUM; CALMODULIN;

D O I：

10.1074/jbc.M113.483107

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In acute and chronic neurodegeneration, Ca2+ mishandling and disruption of the cytoskeleton compromise neuronal integrity, yet abnormalities in the signaling roles of cytoskeletal proteins remain largely unexplored. We now report that the microtubule-associated protein p600 (also known as UBR4) promotes neuronal survival. Following depletion of p600, glutamate-induced Ca2+ influx through NMDA receptors, but not AMPA receptors, initiates a degenerative process characterized by endoplasmic reticulum fragmentation and endoplasmic reticulum Ca2+ release via inositol 1,4,5-trisphosphate receptors. Downstream of NMDA receptors, p600 associates with the calmodulin-calmodulin-dependent protein kinase II alpha complex. A direct and atypical p600/calmodulin interaction is required for neuronal survival. Thus, p600 counteracts specific Ca2+-induced death pathways through regulation of Ca2+ homeostasis and signaling.

引用

页码：24452 / 24464

页数：13

共 53 条

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