Establishment of functional synaptic connections in a selective manner is essential for nervous system operation. In mammalian retinas, rod and cone photoreceptors form selective synaptic connections with different classes of bipolar cells (BCs) to propagate light signals. While there has been progress in elucidating rod wiring, molecular mechanisms used by cones to establish functional synapses with BCs have remained unknown. Using an unbiased proteomic strategy in cone-dominant species, we identified the cell-adhesion molecule ELFN2 to be pivotal for the functional wiring of cones with the ON type of BC. It is selectively expressed in cones and transsynaptically recruits the key neurotransmitter receptor mGluR6 in ON-BCs to enable synaptic transmission. Remarkably, ELFN2 in cone terminals functions in synergy with a related adhesion molecule, ELFN1, and their concerted interplay during development specifies selective wiring and transmission of cone signals. These findings identify a synaptic connectivity mechanism of cones and illustrate how interplay between adhesion molecules and postsynaptic transmitter receptors orchestrates functional synaptic specification in a neural circuit.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519344 | PMC |
| http://dx.doi.org/10.1073/pnas.2009940117 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Generation of three human induced pluripotent stem cell lines from retinitis pigmentosa 25 patient and two carriers but asymptomatic daughters.
Stem Cell Res
December 2024
Ophthalmology Research Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain. Electronic address:
Retinitis Pigmentosa type 25 (RP25) is a form of inherited retinal dystrophy characterized by a progressive loss of rod photoreceptors, subsequent degeneration of cone photoreceptors, and eventually, the retinal pigment epithelium. Caused by mutations in the EYS gene, it is believed to be critical for the structural and functional integrity of the retina. Using a non-integrative RNA reprogramming method, we have generated human induced pluripotent stem cell (hiPSC) lines from RP25 patient and from carriers but asymptomatic daughters.
View Article and Find Full Text PDFStructural and functional dynamics of human cone cGMP-phosphodiesterase important for photopic vision.
Proc Natl Acad Sci U S A
January 2025
Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52242.
Cone cGMP-phosphodiesterase (PDE6) is the key effector enzyme for daylight vision, and its properties are critical for shaping distinct physiology of cone photoreceptors. We determined the structures of human cone PDE6C in various liganded states by single-particle cryo-EM that reveal essential functional dynamics and adaptations of the enzyme. Our analysis exposed the dynamic nature of PDE6C association with its regulatory γ-subunit (Pγ) which allows openings of the catalytic pocket in the absence of phototransduction signaling, thereby controlling photoreceptor noise and sensitivity.
View Article and Find Full Text PDFPleiotropic effects of mutant huntingtin on retinopathy in two mouse models of Huntington's disease.
Neurobiol Dis
December 2024
Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address:
Huntington's disease (HD) is caused by the expansion of a CAG repeat, encoding a string of glutamines (polyQ) in the first exon of the huntingtin gene (HTTex1). This mutant huntingtin protein (mHTT) with extended polyQ forms aggregates in cortical and striatal neurons, causing cell damage and death. The retina is part of the central nervous system (CNS), and visual deficits and structural abnormalities in the retina of HD patients have been observed.
View Article and Find Full Text PDFSyndromic Retinitis Pigmentosa.
Prog Retin Eye Res
December 2024
Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands; Department of Ophthalmology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Retinitis pigmentosa (RP) is a progressive inherited retinal dystrophy, characterized by the degeneration of photoreceptors, presenting as a rod-cone dystrophy. Approximately 20-30% of patients with RP also exhibit extra-ocular manifestations in the context of a syndrome. This manuscript discusses the broad spectrum of syndromes associated with RP, pathogenic mechanisms, clinical manifestations, differential diagnoses, clinical management approaches, and future perspectives.
View Article and Find Full Text PDFAssessment of Photoreceptor Recovery and Visual Function Utilizing Adaptive Optics and Microperimetry in Patients with Surgically Closed Macular Holes.
Photodiagnosis Photodyn Ther
December 2024
Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin, China, Tianjin Key Laboratory of Ocular Trauma, Tianjin, China, Tianjin Institute of Eye Health and Eye Diseases, Tianjin, China, China-UK "Belt and Road" Ophthalmology. Electronic address:
Background: This study investigated the association between photoreceptor structural restoration and visual function outcomes in patients undergoing surgery for closed macular holes (MHs). Using adaptive optics scanning laser ophthalmoscopy (AOSLO) and microperimetry, we aimed to provide a more detailed understanding of photoreceptor recovery and visual improvement in closed MHs.
Methods: We conducted a retrospective observational study of 31 eyes of 28 patients who underwent vitrectomy with internal limiting membrane (ILM) peeling to treat idiopathic MHs.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!