In:
PLOS Biology, Public Library of Science (PLoS), Vol. 20, No. 6 ( 2022-6-16), p. e3001649-
Kurzfassung:
Inherited retinal degeneration due to loss of photoreceptor cells is a leading cause of human blindness. These cells possess a photosensitive outer segment linked to the cell body through the connecting cilium (CC). While structural defects of the CC have been associated with retinal degeneration, its nanoscale molecular composition, assembly, and function are barely known. Here, using expansion microscopy and electron microscopy, we reveal the molecular architecture of the CC and demonstrate that microtubules are linked together by a CC inner scaffold containing POC5, CENTRIN, and FAM161A. Dissecting CC inner scaffold assembly during photoreceptor development in mouse revealed that it acts as a structural zipper, progressively bridging microtubule doublets and straightening the CC. Furthermore, we show that Fam161a disruption in mouse leads to specific CC inner scaffold loss and triggers microtubule doublet spreading, prior to outer segment collapse and photoreceptor degeneration, suggesting a molecular mechanism for a subtype of retinitis pigmentosa.
Materialart:
Online-Ressource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001649
DOI:
10.1371/journal.pbio.3001649.g001
DOI:
10.1371/journal.pbio.3001649.g002
DOI:
10.1371/journal.pbio.3001649.g003
DOI:
10.1371/journal.pbio.3001649.g004
DOI:
10.1371/journal.pbio.3001649.g005
DOI:
10.1371/journal.pbio.3001649.s001
DOI:
10.1371/journal.pbio.3001649.s002
DOI:
10.1371/journal.pbio.3001649.s003
DOI:
10.1371/journal.pbio.3001649.s004
DOI:
10.1371/journal.pbio.3001649.s005
DOI:
10.1371/journal.pbio.3001649.s006
DOI:
10.1371/journal.pbio.3001649.s007
DOI:
10.1371/journal.pbio.3001649.s008
DOI:
10.1371/journal.pbio.3001649.s009
DOI:
10.1371/journal.pbio.3001649.s010
DOI:
10.1371/journal.pbio.3001649.s011
DOI:
10.1371/journal.pbio.3001649.s012
DOI:
10.1371/journal.pbio.3001649.s013
DOI:
10.1371/journal.pbio.3001649.s014
DOI:
10.1371/journal.pbio.3001649.s015
DOI:
10.1371/journal.pbio.3001649.s016
DOI:
10.1371/journal.pbio.3001649.s017
DOI:
10.1371/journal.pbio.3001649.s018
DOI:
10.1371/journal.pbio.3001649.r001
DOI:
10.1371/journal.pbio.3001649.r002
DOI:
10.1371/journal.pbio.3001649.r003
DOI:
10.1371/journal.pbio.3001649.r004
DOI:
10.1371/journal.pbio.3001649.r005
DOI:
10.1371/journal.pbio.3001649.r006
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2022
ZDB Id:
2126773-X
