2. Academic Validation
  3. Ca2+/calmodulin-dependent protein kinase II β decodes ER Ca2+ transients to trigger autophagosome formation

Ca2+/calmodulin-dependent protein kinase II β decodes ER Ca2+ transients to trigger autophagosome formation

  • Mol Cell. 2025 Feb 6;85(3):620-637.e6. doi: 10.1016/j.molcel.2024.12.005.
Qiaoxia Zheng 1,  Huan Zhang 2,  Hongyu Zhao 3,  Yong Chen 3,  Hongzhining Yang 4,  Tingting Li 4,  Qixu Cai 5,  Yingyu Chen 6,  Youjun Wang 7,  Mingjie Zhang 8,  Hong Zhang 9
Affiliations

Affiliations

  • 1 National Laboratory of Biomacromolecules, New Cornerstone Science Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
  • 2 National Laboratory of Biomacromolecules, New Cornerstone Science Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
  • 3 National Laboratory of Biomacromolecules, New Cornerstone Science Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 4 Department of Medical Bioinformatics, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
  • 5 School of Public Health, Xiamen University, Xiamen 361102, China.
  • 6 Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
  • 7 College of Life Sciences, Beijing Normal University, Beijing 100875, China.
  • 8 School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
  • 9 National Laboratory of Biomacromolecules, New Cornerstone Science Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: hongzhang@ibp.ac.cn.
PMID: 39742665 DOI: 10.1016/j.molcel.2024.12.005
Abstract

In multicellular organisms, very little is known about how CA2+ transients on the ER outer surface elicited by Autophagy stimuli are sustained and decoded to trigger autophagosome formation. Here, we show that CA2+/calmodulin-dependent protein kinase II β (CaMKIIβ) integrates ER CA2+ transients to trigger liquid-liquid phase separation (LLPS) of the autophagosome-initiating FIP200 complex. In response to ER CA2+ transients, CaMKIIβ is recruited from actin filaments and forms condensates, which serve as sites for the emergence of or interaction with FIP200 puncta. CaMKIIβ phosphorylates FIP200 at Thr269, Thr1127, and Ser1484 to modulate LLPS and properties of the FIP200 complex, thereby controlling its function in autophagosome formation. CaMKIIβ also controls the amplitude, duration, and propagation of ER CA2+ transients during Autophagy induction. CaMKIIβ mutations identified in the neurodevelopmental disorder MRD54 affect the function of CaMKIIβ in Autophagy. Our study reveals that CaMKIIβ is essential for sustaining and decoding ER CA2+ transients to specify autophagosome formation in mammalian cells.

Keywords

Ca(2+) transient; CaMKIIβ; FIP200; autophagosome; liquid-liquid phase separation.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z