The Hypervariable Region of Atlastin-1 is a Site for Intrinsic and Extrinsic Regulation

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2021 Sep 21

PMID 34546351

Citations 3

Authors

Carolyn M Kelly

Laura J Byrnes

Niharika Neela

Holger Sondermann

John P ODonnell

Affiliations

Soon will be listed here.

Abstract

Atlastin (ATL) GTPases catalyze homotypic membrane fusion of the peripheral endoplasmic reticulum (ER). GTP-hydrolysis-driven conformational changes and membrane tethering are prerequisites for proper membrane fusion. However, the molecular basis for regulation of these processes is poorly understood. Here we establish intrinsic and extrinsic modes of ATL1 regulation that involve the N-terminal hypervariable region (HVR) of ATLs. Crystal structures of ATL1 and ATL3 exhibit the HVR as a distinct, isoform-specific structural feature. Characterizing the functional role of ATL1's HVR uncovered its positive effect on membrane tethering and on ATL1's cellular function. The HVR is post-translationally regulated through phosphorylation-dependent modification. A kinase screen identified candidates that modify the HVR site specifically, corresponding to the modifications on ATL1 detected in cells. This work reveals how the HVR contributes to efficient and potentially regulated activity of ATLs, laying the foundation for the identification of cellular effectors of ATL-mediated membrane processes.

Citing Articles

Dissecting the mechanism of atlastin-mediated homotypic membrane fusion at the single-molecule level.

Shi L, Yang C, Zhang M, Li K, Wang K, Jiao L Nat Commun. 2024; 15(1):2488.

PMID: 38509071 PMC: 10954664. DOI: 10.1038/s41467-024-46919-z.

The atlastin paralogs: The complexity in the tails.

Krishna S, Ford M J Cell Biol. 2023; 222(7).

PMID: 37327452 PMC: 10278267. DOI: 10.1083/jcb.202305116.

Human atlastin-3 is a constitutive ER membrane fusion catalyst.

Bryce S, Stolzer M, Crosby D, Yang R, Durand D, Lee T J Cell Biol. 2023; 222(7).

PMID: 37102997 PMC: 10140384. DOI: 10.1083/jcb.202211021.

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