CRACR2a is a calcium-activated dynein adaptor protein that regulates endocytic traffic.

The Journal of Cell Biology
Yuxiao WangRonald D Vale

Abstract

Cytoplasmic dynein is a minus end-directed microtubule motor that transports intracellular cargoes. Transport is initiated by coiled-coil adaptors that (a) join dynein and its cofactor dynactin into a motile complex and (b) interact with a cargo-bound receptor, which is frequently a Rab GTPase on an organelle. Here, we report two novel dynein adaptors, CRACR2a and Rab45, that have a coiled-coil adaptor domain, a pair of EF-hands, and a Rab GTPase fused into a single polypeptide. CRACR2a-mediated, but not Rab45-mediated, dynein motility is activated by calcium in vitro. In Jurkat T cells, elevation of intracellular calcium activates CRACR2a-mediated dynein transport. We further found that T cell receptor activation induces the formation of CRACR2a puncta at the plasma membrane, which initially associate with the actin cortex and subsequently detach and travel along microtubules, suggestive of an endocytic process. These results provide the first examples of Rab GTPases that directly act as dynein adaptors and implicate CRACR2a-dynein in calcium-regulated endocytic trafficking.

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Citations

May 17, 2019·The Journal of Cell Biology·Katarina T MitevaLynn McKeown
Apr 24, 2019·The Journal of Cell Biology·Mahak Sharma, Devashish Dwivedi
Jun 17, 2020·The FEBS Journal·Yuta HommaMitsunori Fukuda
Nov 12, 2020·Nature Communications·In-Gyun LeeRoberto Dominguez
Dec 4, 2020·Animals : an Open Access Journal From MDPI·Haidong ZhaoXiuzhu Sun
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Xin Xiang, Rongde Qiu
Feb 20, 2021·Scientific Reports·Lucia PediciniLynn McKeown
Apr 3, 2021·Frontiers in Cell and Developmental Biology·Gaël MénaschéUlrich Blank
May 21, 2021·Journal of Cell Science·Amrita KumariSivaram V S Mylavarapu
Jul 25, 2021·International Journal of Molecular Sciences·Takayuki TsukubaTomoko Kadowaki
Jan 11, 2022·The Journal of Cell Biology·Bryony BraschiStephen M King
Jan 6, 2022·Molecular Biology of the Cell·Heidi L AndersonLaura L Lackner

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Methods Mentioned

BETA
GTPases
GTPase
Pulldown
tandem affinity purification
gel filtration
motility assay
FACS
transfection
genotyping

Software Mentioned

ImageJ
Maxchelator
JACoP
MicroManager
Fiji

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