Breaking New Cell Biology Research

To aid their growth, young proteins enlist the protection of a chaperone called BiP (binding immunoglobulin protein), but how our cells make this match has remained unclear. Scientists at the Yale Nanobiology Institute have now decoded the protein signal sequences that determine the movement and timing of the protein-chaperone match – effectively revealing the blueprint for how our proteins reach maturity.

The trans-Golgi Network (TGN) sorts newly synthesized proteins to their destination via vesicular transport carriers. Despite the functional significance of packaging processes at the TGN, the sorting of soluble proteins remains enigmatic. The Golgi resident protein Cab45 is a significant regulator of secretory cargo sorting at the TGN. Cab45 oligomerizes upon transient Ca2+ influx, recruits soluble cargo molecules (clients), and packs them into vesicles. However, the identity of client molecules packed into Cab45 vesicles is scarce. Therefore, we used a highly efficient secretome analysis technology called hiSPECs. Intriguingly, we observed that Cab45 deficient cells manifest hypersecretion of lysosomal hydrolases. Specifically, Cab45 deficient cells secrete the precursors of prosaposin and progranulin. In addition, lysosomes in these cells show an aberrant perinuclear accumulation suggesting a new role of Cab45 in lysosomal positioning.

Synthetic DNA clamps close their jaws to draw tubes from liposomes, resembling the work of membrane-deforming proteins.

Insulin is synthesized by pancreatic β-cells and stored into secretory granules (SGs). The mechanism of how proinsulin and its processing enzymes are sorted and targeted from the trans-Golgi network (TGN) to SGs remains mysterious. No cargo receptor for proinsulin has been identified. Here, we show that chromogranin (CG) proteins undergo liquid-liquid phase separation (LLPS) at a mildly acidic pH in the lumen of the TGN, and recruit clients like proinsulin to the condensates. Client selectivity is sequence-independent but based on the concentration of the client molecules in the TGN. We propose that the TGN provides the milieu for converting CGs into a “cargo sponge,” leading to the partitioning of client molecules, thus facilitating receptor-independent client sorting. These findings provide a new receptor-independent sorting model in β-cells and many other cell types and therefore represent an innovation in the field of membrane trafficking.

In two new papers, scientists provide insight into the function of a protein called VPS13C, one of the molecular suspects that underlie Parkinson’s, a disease marked by uncontrollable movements including tremors, stiffness, and loss of balance.

During polarization of epithelial cells, changes in the lipidome and the expression and distribution of proteins contribute to the formation of apical and basolateral plasma membrane domains. Previous studies utilizing HeLa cells showed that the Syndecan-1 transmembrane domain confers sorting within sphingomyelin-rich vesicles in a sphingomyelin secretion pathway. In polarized MDCK cells, we reveal differences in the sorting of Syndecan-1, whereupon the correct trafficking of the protein is not dependent on its transmembrane domain and changes in sphingomyelin content of cells during polarization. We show that basolateral targeting of Syndecan-1 requires a PDZ motif in Syndecan-1 and the PDZ domain Golgin protein GOPC. Moreover, we reveal changes in Golgi morphology elicited by GOPC overexpression. These results suggest the role of GOPC in sorting Syndecan-1 is indirect and likely due to GOPC effects on Golgi organization.

The manuscript reports the different sorting of ATG9 vesicles and synaptic vesicles in nerve terminals and in an exogenous system

Laboratory researchers may not have sufficient training in the skills needed to form and manage an independent laboratory when they make the transition to Principal Investigator. A group of Yale researchers, including Valentina Greco (SWIM) addressed these challenges using principles from organizational management to navigate the groups and cultural norms of the medical school.

A diverse team of BRCA gene experts work together to unlock the secrets of DNA repair and develop better breast, ovarian and other cancer treatments.