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  2. Cytoskeletal orchestration of glucose uptake in Sertoli cell to support efferocytosis of apoptotic germ cells

Cytoskeletal orchestration of glucose uptake in Sertoli cell to support efferocytosis of apoptotic germ cells

  • Biochim Biophys Acta Mol Cell Res. 2023 Jan 27;119434. doi: 10.1016/j.bbamcr.2023.119434.
Di Wu 1 Nuruliarizki Shinta Pandupuspitasari 2 Kejia Zhang 1 Yuan Tang 1 Faheem Ahmed Khan 3 Haitao Li 1 Chunjie Huang 4 Fei Sun 5
Affiliations

Affiliations

  • 1 Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong 226001, China.
  • 2 Faculty of Animal and Agricultural Sciences, Universitas Diponegoro, Semarang 1269, Indonesia; Department of Biological Engineering, Massachusetts Institute of Technology, MA 02139, USA.
  • 3 Department of Zoology, Faculty of Science and Technology, University of Central Punjab, Lahore 54782, Pakistan; Research Center for Animal Husbandry, National Research and Innovation Agency, Jakarta Pusat 10340, Indonesia.
  • 4 Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong 226001, China. Electronic address: goodlife.huang@ntu.edu.cn.
  • 5 Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong 226001, China. Electronic address: sunfei@ntu.edu.cn.
Abstract

Efferocytosis of non-viable germ cells by Sertoli cells (SCs) constitutes a sentinel for testis homeostasis, yet how SCs signal for the metabolic and cytoskeletal adaption to this energetically costly process remains unexplored. Spectrin is membrane-associated periodic skeleton assembled into an actin-spectrin-based cytoskeletal structure with an interaction with glucose transporter GLUT1. The contribution of spectrin to glucose uptake and efferocytosis is unknown. In this study, we identified a cross-regulation between glucose metabolism and efferocytosis in SCs. Pharmacological or genetic inhibition of glucose uptake or glycolysis compromises efferocytosis activity. We further found that βII-spectrin is a hitherto unappreciated regulator of glucose metabolism and cytoskeletal architecture. βII-spectrin deficiency impairs glucose uptake and lactate production in SCs. Moreover, a defective assembly of Cytoskeleton and a loss of blood-testis barrier integrity are also featured by SCs deficient in βII-spectrin. The disruption in glucose metabolism and cytoskeletal organization synergistically lead to a defective efferocytosis. In vivo siRNA-mediated targeting of βII-spectrin in testis causes an obvious morphological aberration in seminiferous epithelium with the presence of exfoliated germ cells and multinucleated giant cells. Importantly, a decrease in expression of αII/βII-spectrin was observed in testes of Adjudin-induced infertility model. By exploring the functional relevance of βII-spectrin to the metabolic and cytoskeletal regulation of efferocytosis, our study proposes a potential link between βII-spectrin deregulation and male infertility.

Keywords

Cytoskeletal architecture; Efferocytosis; Glucose metabolism; Male infertility; Spectrin.

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