Ral GTPases have long been proposed as regulators of the metazoan exocyst, a conserved secretory vesicle-tethering complex, but direct evidence for this role has been scarce. In contrast, the well-studied yeast exocyst relies on multiple Rab GTPases to regulate function, but yeast do not encode Ral. Using Caenorhabditis elegans, we demonstrate that endogenous RAL-1 directly engages the exocyst through conserved binding sites in its subunits. Loss of RAL-1 disrupts dendritic arborization of PVD sensory neurons, impairs vesicle trafficking, and causes broad developmental defects, acting both cell autonomously in neurons and non-autonomously through supporting epithelial cells. Structure-guided genome editing of RAL-1–exocyst interfaces produced synthetic phenotypes, underscoring the physiological importance of these contacts. Taken together, our findings establish RAL-1 as a bona fide regulator of the metazoan exocyst in vivo and suggest that Ral–exocyst interactions operate in parallel with other secretory pathways. More broadly, this work positions C. elegans as a powerful system to dissect Ral–exocyst mechanisms across molecular, cellular, and developmental scales.
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October 06 2026
The Ral small GTPase is an essential regulator of exocyst complex function in secretion
You Wu
,
You Wu
(Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
Vashisht College of Medicine, Texas A&M Health Science Center, Texas A&M University
, Houston, TX, USA
2
Institute of Biosciences and Technology, Texas A&M Health Science Center, Texas A&M University
, Houston, TX, USA
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David J. Reiner
(Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Supervision, Visualization, Writing - original draft, Writing - review & editing)
1
Vashisht College of Medicine, Texas A&M Health Science Center, Texas A&M University
, Houston, TX, USA
2
Institute of Biosciences and Technology, Texas A&M Health Science Center, Texas A&M University
, Houston, TX, USA
Correspondence to David J. Reiner: [email protected]
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You Wu
https://orcid.org/0009-0004-5535-1091
Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Vashisht College of Medicine, Texas A&M Health Science Center, Texas A&M University
, Houston, TX, USA
2
Institute of Biosciences and Technology, Texas A&M Health Science Center, Texas A&M University
, Houston, TX, USA
David J. Reiner
https://orcid.org/0000-0002-0344-7161
Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Supervision, Visualization, Writing - original draft, Writing - review & editing
1
Vashisht College of Medicine, Texas A&M Health Science Center, Texas A&M University
, Houston, TX, USA
2
Institute of Biosciences and Technology, Texas A&M Health Science Center, Texas A&M University
, Houston, TX, USA
Correspondence to David J. Reiner: [email protected]
Disclosures: The authors declare that no competing interests exist.
Received:
August 28 2025
Revision Received:
May 21 2026
Accepted:
August 20 2026
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funding
Funder(s):
National Institutes of Health
- Award Id(s): R35 GM144237,R03 CA289854,P40 OD010440
© 2026 Wu and Reiner
2026
Wu and Reiner
This article is distributed under the terms as described at https://rupress.org/pages/terms102024/.
J Cell Biol (2026) 225 (11): e202508181.
Article history
Received:
August 28 2025
Revision Received:
May 21 2026
Accepted:
August 20 2026
Citation
You Wu, David J. Reiner; The Ral small GTPase is an essential regulator of exocyst complex function in secretion. J Cell Biol 2 November 2026; 225 (11): e202508181. doi: https://doi.org/10.1083/jcb.202508181
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