Unexpected requirement for a binding partner of the syntaxin family in phagocytosis by murine testicular Sertoli cells
| Autor: | Zhang S, Dong Ys, Liu Db, Hou Wg, Weina Li, Jing Zhao, Liang Gb, Huafeng Zhang, Li Jc, Hao Gz, Yan-Mei Li |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
0301 basic medicine endocrine system Programmed cell death Phagocytosis Vesicular Transport Proteins Biology Cell Line Mice 03 medical and health sciences Downregulation and upregulation medicine Animals Humans Syntaxin Molecular Biology Original Paper Phagocytes Sertoli Cells integumentary system Cell growth Interleukins Intracellular vesicle 3T3 Cells Cell Biology Sertoli cell Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Apoptosis Female ATP Binding Cassette Transporter 1 HeLa Cells Protein Binding |
| Zdroj: | Cell Death & Differentiation. 23:787-800 |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/cdd.2015.139 |
| Popis: | Testicular phagocytosis by Sertoli cells (SCs) plays an essential role in the efficient clearance of apoptotic spermatogenic cells under both physiological and pathological conditions. However, the molecular mechanism underlying this unique process is poorly understood. Herein, we report for the first time that α-taxilin protein (TXLNA), a binding partner of the syntaxin family that functions as a central player in the intracellular vesicle traffic, was dominantly expressed in SCs. Induction of apoptosis in murine meiotic spermatocytes and haploid spermatids by busulfan treatment stimulated a significant increase of TXLNA in SCs at day (d) 14 and d 24 after busulfan treatment, respectively. Consistently, TXLNA expression was steadily upregulated when SCs were co-cultured with apoptotic germ cells (GCs). Moreover, using siRNA treatment, we found that ablation of endogenous TXLNA significantly impaired the phagocytotic capacity of SCs and thereby resulted in defective spermiogenesis and reduced fertility during the late recovery after testicular heat stress. Mechanistically, upregulation of TXLNA expression by apoptotic GCs was associated with the stabilization of ATP-binding cassette transporter 1 (ABCA1), a transporter-mediated lipid efflux from SCs and influencing male fertility. TXLNA acted as an upstream suppressor of ABCA1 ubiquitination and thus promoted ABCA1 stability and accumulation following GC apoptosis. We further provide in vitro evidence that epidermal growth factor receptor (EGFR)-mediated phosphorylation regulated ABCA1 ubiquitination and was enhanced by TXLNA deficiency during testicular phagocytosis. Taken together, the TXLNA/ABCA1 cascade may serve as an important feedback mechanism to modulate the magnitude of subsequent phagocytotic process of SCs in response to testicular injury. |
| Databáze: | OpenAIRE |
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