Fiedler, F. | Search bioRxiv

bioRxiv2023

The N terminus-only (trans) function of the Adhesion GPCR Latrophilin-1 controls multiple processes in reproduction of C. elegans

Adhesion G protein-coupled receptors (aGPCR) are unique molecules. They are able to transmit classical signals via G-protein activation (7TM-dependent/cis signaling) as well as to mediate functions solely through their extracellular N termini, completely independent of the seven transmembrane helices domain (7TM) and the C terminus (7TM-independent/N terminus-only/trans function). This dual mode of action is highly unusual for GPCRs and allows for a plethora of possible cellular consequences. However, the physiological implications and molecular details of this N terminus-mediated signaling are not well understood. Here, we identify three distinct 7TM-independent/trans functions of the aGPCR Latrophilin homolog LAT-1 in the nematode Caenorhabditis elegans together regulating reproduction: sperm guidance, germline apoptosis and proliferative activity of germ cells in the gonadal stem cell niche. In these contexts, the receptor elicits its functions in a non-cell autonomous manner from adjacent somatic cells. These functions might be realized through alternative splicing of the receptor specifically generating N terminus-only variants. Thus, our findings shed light on the versatility of 7TM-independent/N terminus-only/trans functions of aGPCR and discusses possible molecular details.

physiology↗

bioRxiv2022

In situ structural analysis reveals membrane shape transitions during autophagosome formation

Autophagosomes are unique organelles which form de novo as double-membrane vesicles engulfing cytosolic material for destruction. Their biogenesis involves a series of membrane transformations with distinctly shaped intermediates whose ultrastructure is poorly understood. Here, we combine cell biology, correlative cryo-electron tomography (ET) and novel data analysis to reveal the step-by-step structural progression of autophagosome biogenesis at high resolution directly within yeast cells. By mapping individual structures onto a timeline based on geometric features, we uncover dynamic changes in membrane shape and curvature. Moreover, we reveal the organelle interactome of growing autophagosomes, highlighting a polar organization of contact sites between the phagophore and organelles such as the vacuole and the ER. Collectively, these findings have important implications for the contribution of different membrane sources during autophagy and for the forces shaping and driving phagophores towards closure without a templating cargo.

cell biology↗