RESUMEN
Postendocytic sorting of G protein-coupled receptors (GPCRs) is driven by their interactions between highly diverse receptor sequence motifs with their interacting proteins, such as postsynaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), zonula occludens-1 protein (zo-1) (PDZ) domain proteins. However, whether these diverse interactions provide an underlying functional specificity, in addition to driving sorting, is unknown. Here we identify GPCRs that recycle via distinct PDZ ligand/PDZ protein pairs that exploit their recycling machinery primarily for targeted endosomal localization and signaling specificity. The luteinizing hormone receptor (LHR) and ß2-adrenergic receptor (B2AR), two GPCRs sorted to the regulated recycling pathway, underwent divergent trafficking to distinct endosomal compartments. Unlike B2AR, which traffics to early endosomes (EE), LHR internalizes to distinct pre-early endosomes (pre-EEs) for its recycling. Pre-EE localization required interactions of the LHR C-terminal tail with the PDZ protein GAIP-interacting protein C terminus, inhibiting its traffic to EEs. Rerouting the LHR to EEs, or EE-localized GPCRs to pre-EEs, spatially reprograms MAPK signaling. Furthermore, LHR-mediated activation of MAPK signaling requires internalization and is maintained upon loss of the EE compartment. We propose that combinatorial specificity between GPCR sorting sequences and interacting proteins dictates an unprecedented spatiotemporal control in GPCR signal activity.
Asunto(s)
Proteínas de Drosophila/metabolismo , Endocitosis/fisiología , Endosomas/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Receptores Acoplados a Proteínas G/metabolismo , Animales , Homólogo 4 de la Proteína Discs Large , Proteínas de Drosophila/genética , Drosophila melanogaster , Endosomas/genética , Células HEK293 , Células HeLa , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Transporte de Proteínas/fisiología , Receptores Acoplados a Proteínas G/genética , Proteína de la Zonula Occludens-1/genética , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
Image-based sexual abuse (IBSA) refers to the nonconsensual creating, taking, or sharing of intimate images, including threatening to share images. It can also include coercing someone into sharing intimate images, or sending unwanted intimate images. In recent years, there has been growing attention to the nature, scope, and impacts of IBSA, but comparatively little attention has been paid to the perpetration of these harms. This scoping review consolidates and synthesizes the existing knowledge on the perpetration of IBSA against adults. The review involved a systematic search of scholarly and gray literature across select databases. In total, 26 studies met the inclusion criteria. Studies were included if they were published in English between 2013 and 2023 and reported on findings of a sample of adults over the age of 16 who admitted IBSA perpetration behaviors. The review found that prevalence of subtypes of IBSA varied significantly across the studies. There was consensus that adults who engage in IBSA perpetration are more likely to be men, younger adults, and LGBTIQ+. Motivations were multifaceted, but tended to relate to social rewards, power dynamics, sexual gratification, and retaliatory impulses. Dark Tetrad traits were found to be positively associated with IBSA perpetration. The research also indicates on overlap between victimization and perpetration, as well as an association with other offending behaviors, such as intimate partner violence. Prevention interventions should be focused on changing the opportunities, affordances, and infrastructures for offending, as well as addressing problematic societal attitudes and norms, with early interventions focused on building resilience and self-esteem, and promoting healthy behaviors and respectful relationships.
RESUMEN
The laminopathy Hutchinson-Gilford progeria syndrome (HGPS) is caused by the mutant lamin A protein progerin and leads to premature aging of affected children. Despite numerous cell biological and biochemical insights into the basis for the cellular abnormalities seen in HGPS, the mechanism linking progerin to the organismal phenotype is not fully understood. To begin to address the mechanism behind HGPS using Drosophila melanogaster, we have ectopically expressed progerin and lamin A. We found that ectopic progerin and lamin A phenocopy several effects of laminopathies in developing and adult Drosophila, but that progerin causes a stronger phenotype than wild-type lamin A.