Determinants shaping the nanoscale architecture of the mouse rod outer segment.
cell biology
disk rim
membrane curvature
molecular biophysics
mouse
photoreceptor
protein scaffold
rod outer segment
structural biology
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
21 12 2021
21 12 2021
Historique:
received:
05
08
2021
accepted:
09
12
2021
pubmed:
22
12
2021
medline:
22
1
2022
entrez:
21
12
2021
Statut:
epublish
Résumé
The unique membrane organization of the rod outer segment (ROS), the specialized sensory cilium of rod photoreceptor cells, provides the foundation for phototransduction, the initial step in vision. ROS architecture is characterized by a stack of identically shaped and tightly packed membrane disks loaded with the visual receptor rhodopsin. A wide range of genetic aberrations have been reported to compromise ROS ultrastructure, impairing photoreceptor viability and function. Yet, the structural basis giving rise to the remarkably precise arrangement of ROS membrane stacks and the molecular mechanisms underlying genetically inherited diseases remain elusive. Here, cryo-electron tomography (cryo-ET) performed on native ROS at molecular resolution provides insights into key structural determinants of ROS membrane architecture. Our data confirm the existence of two previously observed molecular connectors/spacers which likely contribute to the nanometer-scale precise stacking of the ROS disks. We further provide evidence that the extreme radius of curvature at the disk rims is enforced by a continuous supramolecular assembly composed of peripherin-2 (PRPH2) and rod outer segment membrane protein 1 (ROM1) oligomers. We suggest that together these molecular assemblies constitute the structural basis of the highly specialized ROS functional architecture. Our Cryo-ET data provide novel quantitative and structural information on the molecular architecture in ROS and substantiate previous results on proposed mechanisms underlying pathologies of certain PRPH2 mutations leading to blindness.
Identifiants
pubmed: 34931611
doi: 10.7554/eLife.72817
pii: 72817
pmc: PMC8758146
doi:
pii:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NEI NIH HHS
ID : R01 EY030873
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY030912
Pays : United States
Organisme : NIH HHS
ID : R01EY030912
Pays : United States
Organisme : NIH HHS
ID : R01EY030873
Pays : United States
Informations de copyright
© 2021, Pöge et al.
Déclaration de conflit d'intérêts
MP, JP K.P. is Chief Scientific Officer of Polgenix Inc W.B. holds a position on the advisory board of Thermo Fisher Scientific. All other authors declare no competing interests, JM, SI, KP is Chief Scientific Officer of Polgenix Inc, WB holds a position on the advisory board of Thermo Fisher Scientific
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