The membrane curvature inducing REEP1 proteins generate a novel ER-derived vesicular compartment

Shibata, Y.; Mazur, E. E.; Pan, B.; Hernandez, S. V.; Zhang, J.; Rapoport, T. A.

doi:10.1101/2023.12.19.572386

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bioRxiv · 10.1101/2023.12.19.572386

The membrane curvature inducing REEP1 proteins generate a novel ER-derived vesicular compartment

Shibata, Y.·Mazur, E. E.·Pan, B.·Hernandez, S. V.·Zhang, J.·Rapoport, T. A.

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Abstract

The endoplasmic reticulum (ER) is shaped by abundant, membrane curvature-generating proteins that include the REEP family member REEP5. The REEP1 subfamily, consisting of REEP1-4 in mammals, differs in abundance and topology from REEP5. Mutations in REEP1 and REEP2 cause Hereditary Spastic Paraplegia, but REEP1-4s function remains enigmatic. Here we show that the REEP1 proteins reside in a novel vesicular compartment and identify features that determine their localization. Mutations in REEP1 proteins that compromise curvature-inducing activity, including those that cause disease, relocalize the proteins to the bulk ER. These mutants interact with wildtype proteins to retain them in the ER, consistent with their autosomal-dominant disease inheritance. REEP1vesicles contain the fusogen atlastin-1, but not general ER proteins. We propose that REEP1 proteins generate these vesicles themselves by budding directly from the ER, and that they cycle back to the ER by atlastin-mediated fusion. The vesicles may serve to regulate ER tubule dynamics.

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Shibata, Y., Mazur, E. E., Pan, B., Hernandez, S. V., Zhang, J., Rapoport, T. A.. 2023-12-19. The membrane curvature inducing REEP1 proteins generate a novel ER-derived vesicular compartment. https://doi.org/10.1101/2023.12.19.572386

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