Actin Filaments Take Center Stage in Insulin Secretion

Actin filaments, dynamic architects of cellular function, not only maintain cell structure and drive migration, but also govern the movement of key organelles including mitochondria, lysosomes or, in the case of pancreatic beta cells, insulin secretory granules (ISGs).

In an innovative study recently published in Nature Communications, an international team, drawing on the cryo-ET expertise of Pioneer Campus PI Marion Jasnin, examined the nanoscale intricacies underlying actin remodeling in the context of glucose-stimulated insulin secretion (GSIS).

While actin filaments are known to regulate ISG transport and release under glucose stimulation, fluorescence microscopy suggests that microtubules negatively affect insulin secretion, potentially through their interaction with actin filaments. Yet, due to the limited resolution of fluorescence microscopy, further research is required to elucidate the structural basis of actin remodeling and its interplay with other players during GSIS. Thus, to fully understand the mechanisms governing the inhibitory or facilitatory function of the actin filament network during GSIS, it is imminent to assess and understand the architecture of actin filaments before and after remodeling at the nanoscale.

Solution and Results:
Utilizing a multimodal imaging strategy that incorporates structured illumination microscopy (SIM) and in situ cryo-electron tomography (cryo-ET), the team successfully captured nuanced cellular dynamics both at the periphery and interior of beta cells during GSIS. This comprehensive approach facilitated the visualization and quantitative analysis of actin remodeling during this process, culminating in the development of a model that elucidates the complex actin dynamics at the cell periphery.

By bridging the gap between microscopic visualizations and the nanoscale reality, the study provides a more accurate and detailed depiction of changes in the architecture, alignment, and interaction of actin filaments with ISGs and microtubules during GSIS. The governance of actin filaments in this process, once obscured by the complexities inherent to cellular structures, now takes center stage as a crucial contributor to pancreatic beta cell function. Consequently, this study not only advances our understanding of GSIS but also opens new avenues for diabetes research and potential therapeutic interventions.

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