StripandCkanegatively regulate JNK signalling duringDrosophilaspermatogenesis

Abstract

One fundamental property of a stem cell niche is the exchange of molecular signals between its component cells. Niche models, such as the Drosophila melanogaster testis, have been instrumental in identifying and studying the conserved genetic factors that contribute to niche molecular signalling. Here, we identify jam packed (jam), an allele of Striatin interacting protein (Strip), which is a core member of the highly conserved Striatin-interacting phosphatase and kinase (STRIPAK) complex. In the developing Drosophila testis, Strip cellautonomously regulates the differentiation and morphology of the somatic lineage, and non-cell-autonomously regulates the proliferation and differentiation of the germline lineage. Mechanistically, Strip acts in the somatic lineage with its STRIPAK partner, Connector of kinase to AP-1 (Cka), where they negatively regulate the Jun N-terminal kinase (JNK) signalling pathway. Our study reveals a novel role for Strip/Cka in JNK pathway regulation during spermatogenesis within the developing Drosophila testis.

The Hippo pathway controls myofibril assembly and muscle fiber growth by regulating sarcomeric gene expression

“…However, we find that the core members of the STRIPAK complex Slmap, Strip and Cka as well as Dlg5 are required to regulate Hippo in muscle. Interestingly, Strip and Cka have been shown to bind to each other and regulate either Hippo or other signalling pathways in other Drosophila tissues including eye, testis or motor neurons (La Marca et al, 2019;Neal et al, 2020;Neisch et al, 2017). Slmap appears to be the specific adaptor to link STRIPAK to Hippo in muscle (our work) and epithelia in flies (Neal et al, 2020;Zheng et al, 2017) as well as in mammalian cell culture (Bae et al, 2017;Kwan et al, 2016).…”

The Emerging Roles of JNK Signaling in Drosophila Stem Cell Homeostasis

“…Taken together, these studies reveal that pathological activation of the JNK pathway disrupts morphology, cellular behavior and transcription of somatic cells in the testis. stage because they are improperly encapsulated by mutant somatic cells [32]. Similar phenotypes were observed in the adult testis upon mis-expression of dominant-active JNK or reduction of the endocytic pathway genes in CySCs.…”

“…Despite intensive investigation of numerous conserved signaling networks in the Drosophila testis, JNK was, until recently, underexplored in this tissue. Basal levels of phosphorylated Bsk/JNK and the downstream effectors Puc and Mmp1 are detected in somatic cells of the developing and adult testis but not in GSCs or differentiating germ cells ( Figure 2 A and [ 32 , 33 , 34 , 35 , 36 ]). Individual CySCs homozygous mutant for bsk / JNK cannot self-renew and instead differentiate, suggesting that JNK is required for CySC niche residency under normal conditions [ 35 ].…”

“…However, this result was not observed by another group [ 34 ]. Nevertheless, in CySC self-renewal, JNK is activated by as-yet unidentified intrinsic factors because testes devoid of the ligand Egr/TNFα or Grnd/TNRF do not show alterations in CySC number or in CySC self-renewal [ 32 , 35 ].…”

“…Ultimately, this STRIPAK/JNK/TNFα positive feedback loop disrupts somatic morphology and differentiation. These somatic perturbations have non-autonomous effects on the germline: an increased number of spermatogonia that do not differentiate beyond the transit-amplifying stage because they are improperly encapsulated by mutant somatic cells [ 32 ]. Similar phenotypes were observed in the adult testis upon mis-expression of dominant-active JNK or reduction of the endocytic pathway genes in CySCs.…”