Spatiotemporal regulation of endocytic membrane trafficking by voltage-sensing phosphatase (VSP) in zebrafish enterocytes
Issued Date
2026-05-01
Resource Type
ISSN
03044165
eISSN
18728006
Scopus ID
2-s2.0-105029724249
Journal Title
Biochimica Et Biophysica Acta General Subjects
Volume
1870
Issue
5
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biochimica Et Biophysica Acta General Subjects Vol.1870 No.5 (2026)
Suggested Citation
Ratanayotha A., Mizutani N., Takenaga F., Kawai T., Okamura Y. Spatiotemporal regulation of endocytic membrane trafficking by voltage-sensing phosphatase (VSP) in zebrafish enterocytes. Biochimica Et Biophysica Acta General Subjects Vol.1870 No.5 (2026). doi:10.1016/j.bbagen.2026.130916 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115126
Title
Spatiotemporal regulation of endocytic membrane trafficking by voltage-sensing phosphatase (VSP) in zebrafish enterocytes
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Author's Affiliation
Corresponding Author(s)
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Abstract
In developing vertebrates, nutrient uptake by specialized epithelial cells is primarily mediated by endocytosis, a process driven by dynamic phosphoinositide remodeling that regulates vesicle formation and endosomal maturation. Voltage-sensing phosphatase (VSP), a unique membrane protein that couples changes in membrane potential to phosphoinositide hydrolysis, is expressed in zebrafish lysosome-rich enterocytes (LREs), which mediate endocytosis-dependent nutrient absorption during development. However, the molecular mechanisms by which zebrafish VSP (Dr-VSP) regulates endocytic membrane trafficking remain unclear. Here, we elucidate by confocal imaging that Dr-VSP localizes to subapical endomembranes and dynamically redistributes to the apical plasma membrane during nutrient uptake, where it promotes early vesicle formation and maintains proper endolysosomal organization. Loss of Dr-VSP reduces early endocytic vesicles and disrupts downstream recycling and lysosomal compartments, leading to defective nutrient absorption. Electrophysiological analyses showed that extracellular or luminal acidic pH suppresses Dr-VSP voltage sensing, consistent with its activity being confined to the apical plasma membrane where voltage, pH, and phosphoinositide conditions are favorable for activation. These findings indicate that Dr-VSP acts as a voltage- and pH-regulated phosphoinositide phosphatase during the early phase of endocytosis at the plasma membrane, preceding lysosomal digestion. This work defines a functional role for VSPs in epithelial nutrient uptake in vertebrate enterocytes and points to a novel electrochemical mechanism underlying membrane trafficking in vertebrates.