Unexpected requirement for a binding partner of the syntaxin family in phagocytosis by murine testicular Sertoli cells.
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.
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, Shenyang 110016, China.|Department of Histology and Embryology, Fourth Military Medical University, Xi'an 710032, China.
Y-s
YS
Dong
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
W-g
WG
Hou
Department of Air Logistics, 463rd Hospital of PLA, Shenyang 110042, China.
Y
Y
Li
Department of Air Logistics, 463rd Hospital of PLA, Shenyang 110042, China.
D-b
DB
Liu
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, Shenyang 110016, China.
G-z
GZ
Hao
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, Shenyang 110016, China.
H-f
HF
Zhang
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, Shenyang 110016, China.
J-c
JC
Li
Department of Histology and Embryology, Fourth Military Medical University, Xi'an 710032, China.
J
J
Zhao
Department of Gynecology and Obstetrics, Reproductive Medicine Center, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
S
S
Zhang
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, Shenyang 110016, China.
G-b
GB
Liang
Department of Histology and Embryology, Fourth Military Medical University, Xi'an 710032, China.
W
W
Li
D016475:3T3 Cells; D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000378:metabolism*; D010587:Phagocytosis; D011485:Protein Binding; D012708:Sertoli Cells / Q000166:cytology* / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D064286:ATP Binding Cassette Transporter 1; D007378:Interleukins; D033921:Vesicular Transport Proteins; C577833:Abca1 protein, mouse; C545985:TXLNA protein, mouse