Chromatin remodeling complexes control the availability of DNA binding sites to transcriptional regulators. Two distinct forms of the major SWI/SNF-related complex that have different activities in vitro can be distinguished by the presence of specific accessory subunits. In Drosophila, the core Brahma complex associates either with Osa to form the BAP complex, or with Bap170 and Bap180 to form the PBAP complex. Mutations affecting the core subunits have stronger developmental phenotypes than osa mutations; these differences could be due to PBAP complex activity . We have generated mutations in the genes encoding the PBAP-specific subunits Bap170 and Bap180 in order to study their functions in vivo. Bap180 is not essential for viability, but is required in ovarian follicle cells for normal eggshell development. Bap170 is necessary to stabilize the Bap180 protein; however, a mutant form that retains this function is sufficient for survival and fertility. The two subunits act redundantly to allow metamorphosis; using gene expression profiling of double mutants, we have found that the PBAP complex regulates genes involved in tissue remodeling and immune system function. Finally, we have generated mutants that lack Bap170, Bap180 and Osa in the germline to demonstrate that the function of the core Brahma complex in oogenesis does not require any of these accessory subunits.
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View SamplesCD8+ tumor infiltrating T cells (TIL) lack effector-phase functions due to defective proximal TCR-mediated signaling shown to result from inactivation of p56lck kinase. We identify a novel interacting partner for p56lck in nonlytic TIL, Protocadherin-18 (pcdh18), and show that pcdh18 is transcribed upon in vitro or in vivo activation of CD8+ central memory T cells (CD44+CD62LhiCD127+) coincident with conversion into effector memory cells (CD44+CD62LloCD127+). Expression of pcdh18 in primary CD8+ effector cells induces the phenotype of nonlytic TIL: defective; proximal TCR signaling, cytokine secretion, and cytolysis; and enhanced AICD. pcdh18 contains a motif (centered at Y505) shared with src kinases (QGQYQP) which is required for the inhibitory phenotype. Thus, pcdh18 is a novel marker of CD8+ effector memory T cells expressed upon cell activation that can function as a negative regulator by restricting the effector phase.
Protocadherin-18 is a novel differentiation marker and an inhibitory signaling receptor for CD8+ effector memory T cells.
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