Biology subjects

Jentsch, S.

Publications and source records attributed to Jentsch, S..

2 recordsLinked to original sources

bioRxiv2020

ESCRT recruitment by the inner nuclear membrane protein Heh1 is regulated by Hub1-mediated alternative splicing

Misassembled nuclear pore complexes (NPCs) are removed by sealing off the surrounding nuclear envelope (NE), which is mediated by members of the ESCRT (endosomal sorting complexes required for transport) machinery. Recruitment of ESCRT proteins to the NE is mediated by the interaction between the ESCRT member Chm7 and the inner nuclear membrane protein Heh1, which belongs to the conserved LEM family. Increased ESCRT recruitment results in excessive membrane scission at damage sites but its regulation remains poorly understood. Here, we show that Hub1-mediated alternative splicing of HEH1 pre-mRNA, resulting into its shorter form Heh1-S, is critical for the integrity of the NE. ESCRT-III mutants lacking Hub1 or Heh1-S display severe growth defects and accumulate improperly assembled NPCs. This depends on the interaction of Chm7 with the conserved MSC domain only present in the longer spliced variant Heh1-L. Heh1 variants assemble into heterodimers and we demonstrate that a unique splice segment in Heh1-S suppresses growth defects associated with uncontrolled interaction between Heh1-L and Chm7. Together, our findings reveal that Hub1-mediated splicing generates Heh1-S to regulate ESCRT recruitment to the nuclear envelope. Summary statementHeh1-S, the Hub1-mediated spliced version of HEH1 pre-mRNA, contributes to nuclear envelope maintenance by preventing excessive recruitment of Chm7.

cell biology↗

bioRxiv2020

A selective autophagy pathway for phase separated endocytic protein deposits

Autophagy eliminates cytoplasmic content selected by autophagy receptors, which link cargoes to the membrane bound autophagosomal ubiquitin-like protein Atg8/LC3. Here, we discover a selective autophagy pathway for protein condensates formed by endocytic proteins. In this pathway, the endocytic yeast protein Ede1 functions as a selective autophagy receptor. Distinct domains within Ede1 bind Atg8 and mediate phase separation into condensates. Both properties are necessary for an Ede1-dependent autophagy pathway for endocytic proteins, which differs from regular endocytosis, does not involve other known selective autophagy receptors, but requires the core autophagy machinery. Cryo-electron tomography of Ede1-containing condensates - at the plasma membrane and in autophagic bodies - shows a phase-separated compartment at the beginning and end of the Ede1-mediated selective autophagy pathway. Our data suggest a model for autophagic degradation of membraneless compartments by the action of intrinsic autophagy receptors. HighlightsO_LIEde1 is a selective autophagy receptor for aberrant CME protein assemblies C_LIO_LIAberrant CME assemblies form by liquid-liquid phase separation C_LIO_LICore autophagy machinery and Ede1 are important for degradation of CME condensates C_LIO_LIUltrastrucural view of a LLPS compartment at the PM and within autophagic bodies C_LI

cell biology↗