Mazurkiewicz, M. | Search bioRxiv

bioRxiv2025

Tmem117, an oligodendrocyte-enriched regulator of NCX activity, links myelin homeostasis to counterregulation and metabolic health.

The counterregulatory response (CRR) to hypoglycemia is a fundamental, evolutionarily conserved homeostatic mechanism orchestrated by the central nervous system (CNS) to ensure survival during glucose scarcity. In individuals with diabetes, this response is frequently impaired, contributing to life-threatening episodes of hypoglycemia. Tmem117 was previously identified in a genetic screen as a promising hypothalamic regulator of CRR. Our previous work highlighted its contribution to CRR through regulation of vasopressin secretion. Here, we reveal that Tmem117 is also enriched in cells of the oligodendrocytic lineage and we characterize the contribution of oligodendrocytic Tmem117 in CRR. We show that depletion of Tmem117 from either all oligodendrocyte lineage cells or only mature oligodendrocytes leads to myelin deficits and male-specific defects in CRR. Furthermore, we reveal that transient, adult-onset depletion of Tmem117 in mature oligodendrocytes is sufficient to induce long-lasting metabolic imbalances in male mice, suggesting that defects in oligodendrocytes and myelin can affect peripheral glucose homeostasis. Mechanistically, we provide for the first-time insights on the function of Tmem117 showing that it regulates intracellular calcium dynamics through its interaction with the sodium-calcium exchanger NCX1. Together, these results redefine our understanding of the cellular contributors to the CRR, highlight the importance of oligodendrocytes in systemic glucose regulation, and position Tmem117 as a promising molecular target for cell-specific manipulation of NCX activity.

neuroscience↗

bioRxiv2023

High resolution longitudinal molecular and morphological tracking of planktonic threats to salmon aquaculture.

Marine-phase salmonid aquaculture is a major component of the coastal economies of Northern Europe, North America and Chile and is under threat from numerous challenges to gill health, many of which originate from the phyto- and zooplankton. Associated losses are growing as a proportion of production year on year. A first step towards mitigating losses is to characterize the biological drivers of poor gill health. Numerous planktonic species have been implicated, including toxic and siliceous microalgae, hydrozoans and scyphozoans; however, rigorous longitudinal surveys of planktonic diversity and gill health have been lacking. In the current study, we present and assess an exhaustive identification approach combining both morphological and molecular methods (environmental DNA metabarcoding) approaches in combination with robust statistical models to identify the planktonic drivers of complex gill disease (CGD) and fish mortality. We undertook longitudinal molecular and microscopic evaluation at two marine aquaculture facilities on the west coast of Scotland using daily data collected during the 2021 growing season (March-October). Examining these two different sites, one sheltered and one exposed to the open sea, we identified new, important, and unexpected planktonic drivers (e.g. doliolids and appendicularians) of CGD and mortality and confirmed the significance of some established threats (e.g. hydrozoans and diatoms). We also explored delayed or lagged effects of planktonic abundances on gill health and undertook a comparison of environmental DNA metabarcoding and microscopy in their ability to identify and quantify planktonic species. Our data highlight the diversity of planktonic threats to salmonid aquaculture as well as the importance of using both molecular and morphological approaches to detect those. Despite our study relying on two farm sites only, our results evidence the role of the different planktonic players on salmon gill disease; there is now an urgent need to expand systematic longitudinal molecular and morphological approach across multiple sites and over multiple years. The resultant catalogue of main biological drivers will enable early warning systems, new treatments and, ultimately, a sustainable platform for future salmonid aquaculture in the marine environment.

zoology↗