In mammals, spermatogenesis is a multistep processes, comprising mitotic proliferation of spermatogonia, meiotic division of spermatocytes and maturation of haploid spermatids (Nakanishi

INTRODUCTION In mammals, spermatogenesis is a multistep processes, comprising mitotic proliferation of spermatogonia, meiotic division of spermatocytes and maturation of haploid spermatids (Nakanishi and Shiratsuchi, 2004). As spermatids undergo terminal differentiation into spermatozoa, the bulk cytoplasmic contents are segregated into the residual body, which is sloughed off, phagocytosed and degraded by Sertoli cells (Breucker et al., 1985; Blanco-Rodríguez and Martinez-Garcia, 1999). In C. elegans, spermatogenesis occurs in both males and hermaphrodites (Schedl, 1997). Upon entering meiosis, primary spermatocytes (spermatogonia) bud off the syncytial cytoplasmic core, known as the rachis, and undergo the first meiotic division, resulting in the generation of two secondary spermatocytes that may or may not remain attached by a cytoplasmic bridge (Ward, 1986). Nevertheless, the resulting secondary spermatocytes initiate meiosis II to produce two haploid spermatids and one residual body (Fig. 1A). The cytosolic components are differentially partitioned into developing spermatids and the residual body. Spermatids inherit mitochondria, Golgi-derived fibrous-body membranous organelles (FB-MOs) and a haploid nucleus, whereas all ribosomes, nearly all actin and myosin and most of the tubulin, are packaged into the residual body (Ward, 1986; Ward et al., 1983; Machaca et al., 1996). C. elegans spermatogenesis occurs in the absence of cells functioning as Sertoli cells, which separate different stages of spermatogenesis into distinct compartments in mammals (Nakanishi and Shiratsuchi, 2004). Little is known about the molecular and cellular mechanisms underlying the clearance of residual bodies. During C. elegans development, 131 somatic cells undergo apoptosis and the apoptotic cell corpses are removed by neighboring cells (Sulston and Horvitz, 1977; Sulston et al., 1983). Following recognition of the ‘eat me’ signal phosphatidylserine (PS) on the surface of cell corpses, phagocytic cells extend pseudopods, then envelop and internalize the cell corpse to form a phagosome (Zhou and Yu, 2008; Kinchen and Ravichandran, 2008). Recognition and phagocytosis of cell corpses are mediated by two partially redundant signaling pathways with psr-1, ina-1, ced-2, ced-5, ced-12 and ced-10 in one pathway and ttr-52, ced-1, ced-7, ced-6 and dyn-1 in the other (Fig. 1B) (Zhou and Yu, 2008; Kinchen and Ravichandran, 2008; Yu et al., 2006; Wang et al., 2010; Hsu and Wu, 2010; Wang et al., 2003). CED-2 (CrkII in mammals), CED-5 (Dock180; also known as Dock1) and CED-12 (ELMO) mediate the engulfment signal received by upstream receptors such as PSR-1 and INA-1 to activate CED-10 (Rac1), which regulates the cytoskeleton rearrangement of engulfing cells (Reddien and Horvitz, 2000; Wu and Horvitz, 1998b; Wu et al., 2001; Zhou et al., 2001a; Gumienny et al., 2001). The secreted bridging molecule TTR-52, transmembrane scavenger-receptor-like protein CED-1 (mammalian LRP1/MEGF10), an ATP-binding cassette transporter CED-7 (ABCA1 and ABCA7) and the secreted LPS-binding/lipid transfer family protein NRF-5 regulate the initial recognition of apoptotic cells. The signal is transduced by the adaptor protein CED-6 (GULP), which may also converge on CED-10 to coordinately regulate the actin cytoskeleton (Wang et al., 2010; Zhou et al., 2001b; Liu and Hengartner, 1998; Wu and Horvitz, 1998a; Kinchen et al., 2005; Zhang et al., 2012). Maturation of nascent cell corpse-containing phagosomes involves dynamic association of PdtIns(3)P and sequential recruitment of Rab small GTPases, including RAB-5, RAB-7, UNC-108/RAB2 and RAB-14, that mediate the stepwise maturation processes, 1State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, P.R. China. 2Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center, Beijing, 100191, P.R. China. 3College of Life Sciences, China Agricultural University, Beijing, 100094, P.R. China. 4National Institute of Biological Sciences, Beijing, 102206, P.R. China.