A role for CASM in the repair of damaged Golgi architecture

Seeun Oh1, Saif Ullah1, Bhaskar Saha1,2

  • 1Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.

Autophagy
|May 12, 2026
PubMed

Insights

Cellular asymmetric membrane (CASM) response preserves Golgi apparatus integrity by coordinating lysosomal biogenesis and lipid conjugation, aiding cellular homeostasis after membrane damage.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • The cellular asymmetric membrane (CASM) process involves lipid conjugation of Atg8-family proteins to damaged endomembranes, but its role in cellular homeostasis remains unclear.
  • TRIM46, a ubiquitin ligase, influences microtubule organization and Golgi apparatus structure.

Purpose of the Study:

  • To investigate the role of CASM in maintaining Golgi apparatus architecture, particularly after the loss of TRIM46.
  • To elucidate the mechanisms by which CASM contributes to cellular homeostasis in response to membrane damage.

Main Methods:

  • Utilized TRIM46-deficient cell models to observe Golgi morphology and Atg8-family protein localization.
  • Investigated the impact of genetic inhibition of CASM on TFEB activation and Golgi structure.
  • Assessed Golgi reformation capacity following drug-induced fragmentation in cells with reduced CASM gene expression.

Main Results:

  • TRIM46 deficiency led to Golgi ribbon fragmentation and enhanced TFEB-driven lysosomal biogenesis, with Atg8-family proteins localizing to the Golgi.
  • Golgi Atg8ylation in TRIM46-deficient cells mimicked CASM and was non-degradative.
  • Inhibiting CASM in TRIM46-deficient cells worsened Golgi defects and reduced TFEB activation, indicating CASM's role in Golgi repair.
  • Knockdown of CASM genes impaired Golgi reformation after drug-induced fragmentation.

Conclusions:

  • CASM is a crucial component of the Golgi damage response, acting to preserve Golgi integrity.
  • Lysosomal biogenesis and CASM are coordinated processes involved in repairing Golgi apparatus damage.
  • The study identifies a novel role for CASM in maintaining Golgi homeostasis.

Related Concept Videos

Golgi Matrix Proteins01:12

Golgi Matrix Proteins

Golgi matrix proteins are a group of highly dynamic proteins that maintain the stacked structure of Golgi. These proteins adapt to rapid morphological changes of the Golgi during the cell cycle. During cell division, mild proteolysis removes these connections resulting in Golgi unstacking. In The daughter cells, these proteins help reassemble the unstacked Golgi.
One of the first identified Golgi matrix proteins was GM130, a rod-like protein located in the cis-Golgi. Subsequently, many Golgi...
Transport Across the Golgi01:26

Transport Across the Golgi

While it is unclear how molecules move between adjacent Golgi cisternae, it is apparent that the molecules move from cis- cisterna, the entry face, to the trans- cisterna, the exit face. Experiments initially suggested vesicles that bud from one cisterna and fuse with the next cisterna to transport proteins between the cisternae. This vesicular transport model describes the Golgi apparatus as a relatively static structure with a unique enzyme composition in each cisterna. Molecules are...
Golgi Apparatus01:49

Golgi Apparatus

As they leave the Endoplasmic Reticulum (ER), properly folded and assembled proteins are selectively packaged into vesicles. These vesicles are transported by microtubule-based motor proteins and fuse together to form vesicular tubular clusters, subsequently arriving at the Golgi apparatus, a eukaryotic endomembrane organelle that often has a distinctive ribbon-like appearance.
Golgi Apparatus01:09

Golgi Apparatus

Properly folded and assembled proteins are selectively packaged into vesicles that exit the ER. Motor proteins transport these vesicles to the Golgi apparatus for adding modifications that make these proteins functional at their destination.
The Golgi apparatus is a eukaryotic organelle that has a distinctive ribbon-like appearance. It is a primary sorting and dispatch station for cargo arriving from the ER. Newly arriving vesicles enter the cis face of the Golgi, closest to the ER, and are...
Golgi Apparatus01:09

Golgi Apparatus

Properly folded and assembled proteins are selectively packaged into vesicles that exit the ER. Motor proteins transport these vesicles to the Golgi apparatus for adding modifications that make these proteins functional at their destination.
The Golgi apparatus is a eukaryotic organelle that has a distinctive ribbon-like appearance. It is a primary sorting and dispatch station for cargo arriving from the ER. Newly arriving vesicles enter the cis face of the Golgi, closest to the ER, and are...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...