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bioRxiv · 10.64898/2026.07.15.737746

SH3KBP1/CIN85, a new actor of ER-phagy in muscle

Daura, M.·Vergara, E.·Andromaque, L.·Leddet, A.·Christin, E.·Malleval, C.·Gache, V.·Kretz-Remy, C.
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Abstract

The endoplasmic reticulum (ER) and its muscle-specialized form, the sarcoplasmic reticulum (SR), are crucial organelles in muscle cells, involved notably in protein synthesis, calcium regulation and muscle contraction. A well-known process involved in ER remodeling and homeostasis is ER-phagy, also called reticulophagy, a selective form of autophagic process in which ER-phagy receptors mediate the delivery of ER portions to lysosomes for degradation. SH3KBP1 is an adaptor protein involved in membrane trafficking. Recently, it was shown to control ER morphology and SR formation in striated skeletal muscle. In this study, we demonstrate that SH3KBP1 can bind to LC3B and CKAP4 proteins, bridging ER to autophagosome membranes, and is degraded by autophagy, in developing muscle fibers. Moreover, SH3KBP1 down-regulation impacts basal autophagy efficiency and ER-phagy stimulation; it also impairs the turnover of numerous ER-resident proteins. Our work highlights a new role for SH3KBP1 as a soluble ER-phagy receptor in striated skeletal muscle.

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Daura, M., Vergara, E., Andromaque, L., Leddet, A., Christin, E., Malleval, C., Gache, V., Kretz-Remy, C.. 2026-07-15. SH3KBP1/CIN85, a new actor of ER-phagy in muscle. https://doi.org/10.64898/2026.07.15.737746

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