The Absence of FAIM Leads to a Delay in Dark Adaptation and Hampers Arrestin-1 Translocation upon Light Reception in the Retina
Sirés, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Pazo-González, Mateo (Universidad de Alcalá)
López-Soriano, Joaquín (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Méndez, Ana (Institut d'Investigació Biomèdica de Bellvitge)
de la Rosa, Enrique J. (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
de la Villa, Pedro (Universidad de Alcalá)
Comella i Carnicé, Joan Xavier 1963- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Hernández-Sánchez, Catalina (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Solé Piñol, Montserrat (Hospital Universitari Vall d'Hebron. Institut de Recerca)

Date:	2023
Abstract:	The short and long isoforms of FAIM (FAIM-S and FAIM-L) hold important functions in the central nervous system, and their expression levels are specifically enriched in the retina. We previously described that Faim knockout (KO) mice present structural and molecular alterations in the retina compatible with a neurodegenerative phenotype. Here, we aimed to study Faim KO retinal functions and molecular mechanisms leading to its alterations. Electroretinographic recordings showed that aged Faim KO mice present functional loss of rod photoreceptor and ganglion cells. Additionally, we found a significant delay in dark adaptation from early adult ages. This functional deficit is exacerbated by luminic stress, which also caused histopathological alterations. Interestingly, Faim KO mice present abnormal Arrestin-1 redistribution upon light reception, and we show that Arrestin-1 is ubiquitinated, a process that is abrogated by either FAIM-S or FAIM-L in vitro. Our results suggest that FAIM assists Arrestin-1 light-dependent translocation by a process that likely involves ubiquitination. In the absence of FAIM, this impairment could be the cause of dark adaptation delay and increased light sensitivity. Multiple retinal diseases are linked to deficits in photoresponse termination, and hence, investigating the role of FAIM could shed light onto the underlying mechanisms of their pathophysiology.
Grants:	Ministerio de Sanidad y Consumo CB06/05/1104
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Retina ; Rod photoreceptors ; Arrestin-1 ; FAIM ; Dark adaptation ; Ubiquitin ; Light damage ; Knockout mouse model
Published in:	Cells, Vol. 12 (february 2023) , ISSN 2073-4409

DOI: 10.3390/cells12030487
PMID: 36766830

28 p, 5.6 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles