bims-lycede 2025-11-09 papers

Dev Cell. 2025 Nov 03. pii: S1534-5807(25)00604-5. [Epub ahead of print]60(21): 2841-2843

Golgiphagy mediated by TM9SF3 acts as quality control for stressed Golgi.

Selective autophagy is important for organelle quality control. In this issue of Developmental Cell, Yang et al. identify the Golgi resident transmembrane protein TM9SF3 as a selective autophagy receptor required for lysosomal degradation of Golgi fragments (Golgiphagy) following nutrient stress, pH disruption, blockade of ER-to-Golgi trafficking, and defects in Golgi-mediated glycosylation functions.

DOI: https://doi.org/10.1016/j.devcel.2025.09.019

Genes Cells. 2025 Nov;30(6): e70063

Cell Surface LAMP-2C Is Internalized in a Clathrin-Dependent Manner and Transported to the Recycling and Lysosomal Pathways.

Hiroshi Sakane, Yuna Takeda, Ikuto Okuda, Kanae Michihara, Kenji Akasaki.

Lysosomes are acidic organelles that degrade a diverse range of substrates, and lysosome-associated membrane protein (LAMP)-1 and LAMP-2 are the major lysosomal membrane components. Three LAMP-2 splice variants have been identified, namely, LAMP-2A, LAMP-2B, and LAMP-2C. We previously demonstrated that when mouse LAMP-2C was stably expressed in HEK293 cells, a portion of it was present on the plasma membrane. LAMP-2C possesses a tyrosine-based motif that functions as a signal for lysosomal targeting and clathrin-mediated endocytosis (CME). However, whether cell surface LAMP-2C is indeed internalized via CME has not been clearly defined. If this occurs, it is unknown whether internalized LAMP-2C returns to the cell surface and/or moves to lysosomes from early endosomes. In this study, we found that cell surface LAMP-2C was internalized, and its internalization was impaired by knockdown of the clathrin heavy chain or the medium subunit of adaptor protein complex 2. Internalized LAMP-2C was transported to early endosomes, and a portion of the internalized LAMP-2C was recycled back to the plasma membrane. Furthermore, immunofluorescence and subcellular fractionation showed that the internalized LAMP-2C was transported to lysosomes. These results suggest that cell surface LAMP-2C is internalized by CME and that internalized LAMP-2C enters the recycling and lysosomal pathways.

Keywords: LAMP‐2; clathrin; lysosome; recycling

DOI: https://doi.org/10.1111/gtc.70063

Nature. 2025 Nov 05.

Secretome translation shaped by lysosomes and lunapark-marked ER junctions.

Heejun Choi, Ya-Cheng Liao, Young J Yoon, Jonathan Grimm, Nan Wang, Luke D Lavis, Robert H Singer, Jennifer Lippincott-Schwartz.

The endoplasmic reticulum (ER) is a highly interconnected membrane network that serves as a central site for protein synthesis and maturation1. A crucial subset of ER-associated transcripts, termed secretome mRNAs, encode secretory, lumenal and integral membrane proteins, representing nearly one-third of human protein-coding genes1. Unlike cytosolic mRNAs, secretome mRNAs undergo co-translational translocation, and thus require precise coordination between translation and protein insertion2,3. Disruption of this process, such as through altered elongation rates4, activates stress response pathways that impede cellular growth, raising the question of whether secretome translation is spatially organized to ensure fidelity. Here, using live-cell single-molecule imaging, we demonstrate that secretome mRNA translation is preferentially localized to ER junctions that are enriched with the structural protein lunapark and in close proximity to lysosomes. Lunapark depletion reduced ribosome density and translation efficiency of secretome mRNAs near lysosomes, an effect that was dependent on eIF2-mediated initiation and was reversed by the integrated stress response inhibitor ISRIB. Lysosome-associated translation was further modulated by nutrient status: amino acid deprivation enhanced lysosome-proximal translation, whereas lysosomal pH neutralization suppressed it. These findings identify a mechanism by which ER junctional proteins and lysosomal activity cooperatively pattern secretome mRNA translation, linking ER architecture and nutrient sensing to the production of secretory and membrane proteins.

DOI: https://doi.org/10.1038/s41586-025-09718-0