Journal of Cell Biology最新文献

Septins can assemble into scaffolds at the plasma membrane to regulate cell morphology. While septins preferentially bind convex membranes via amphipathic helices, their assembly on varied geometries in cells suggests additional localization cues. We tested the hypothesis that lipid composition directs septin assembly through the property of lipid packing. We used pharmacological perturbations that alter fatty acid chain saturation to manipulate lipid packing and found septin structures were selectively disrupted at flat regions of the plasma membrane. To determine whether lipid packing is sufficient to impact septin assembly, molecular dynamics simulations were used to design lipid mixtures with varied packing to monitor septin adsorption in vitro. Septins strongly favored loosely packed lipid bilayers, but additional geometrical cues act in conjunction with this membrane property. This work demonstrates that packing defects and geometry jointly regulate septin localization, highlighting how distinct membrane properties are integrated to organize the septin cytoskeleton.

Recent advances in quantitative bioimage analysis have enabled detailed analyses of cellular and subcellular morphological features, enhancing our understanding of cellular functions. Here, we introduce an image-based phenotyping pipeline designed for the comprehensive analysis of dynamic organelle morphology, particularly the Golgi apparatus and cilia, during cell cycle progression. Our approach emphasizes interpretable feature extraction, enabling detection of both prominent and subtle morphological changes. By using well-characterized morphological dynamics of intracellular structures as benchmarks, we demonstrated that our method can reliably detect established phenotypic changes and serves as a valid tool for quantitative profiling. Further investigation of the G0/G1 transition revealed an unexplored link between Golgi dynamics and ciliary disassembly. Specifically, inhibition of the G0/G1 transition correlated with ciliary persistence and unique Golgi dispersion, involving Aurora kinase A (AURKA). Our results thus indicate an association of Golgi morphology with cell cycle reentry and ciliary dynamics, underscoring the value of our profiling method in studying cellular regulation in health and disease.

Unconventional protein secretion (UcPS) exports diverse signal peptide-lacking cargoes, yet its cargo selectivity remains poorly understood. Here, we identify TMED proteins as key regulators of vesicle-dependent UcPS, mediating selective cargo release via translocation into secretory carriers. TMED proteins act as translocators, facilitating cargo passage across lipid bilayers with assistance from HSP90 chaperones and partial cargo unfolding. Selectivity arises during translocation, where TMED cytoplasmic tails bind specific cargoes. The ER-Golgi intermediate compartment (ERGIC) is essential for TMED-mediated translocation and release. TMED homo-oligomerization enhances translocation, while hetero-tetramerization inhibits it. ERGIC localization promotes homo-oligomerization, which is further stabilized by cargo binding, forming a feed-forward mechanism to enhance translocation. These findings establish TMED proteins as central regulators of cargo diversity in UcPS, with their oligomerization and subcellular localization modulating translocation efficiency.