Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome

X Shi, G Garcia III, JC Van De Weghe, R McGorty… - Nature cell …, 2017 - nature.com
Nature cell biology, 2017nature.com
Abstract Ciliopathies, including nephronophthisis (NPHP), Meckel syndrome (MKS) and
Joubert syndrome (JBTS), can be caused by mutations affecting components of the
transition zone, a domain near the base of the cilium that controls the protein composition of
its membrane. We defined the three-dimensional arrangement of key proteins in the
transition zone using two-colour stochastic optical reconstruction microscopy (STORM).
NPHP and MKS complex components form nested rings comprised of nine-fold doublets …
Abstract
Ciliopathies, including nephronophthisis (NPHP), Meckel syndrome (MKS) and Joubert syndrome (JBTS), can be caused by mutations affecting components of the transition zone, a domain near the base of the cilium that controls the protein composition of its membrane. We defined the three-dimensional arrangement of key proteins in the transition zone using two-colour stochastic optical reconstruction microscopy (STORM). NPHP and MKS complex components form nested rings comprised of nine-fold doublets. JBTS-associated mutations in RPGRIP1L or TCTN2 displace certain transition-zone proteins. Diverse ciliary proteins accumulate at the transition zone in wild-type cells, suggesting that the transition zone is a waypoint for proteins entering and exiting the cilium. JBTS-associated mutations in RPGRIP1L disrupt SMO accumulation at the transition zone and the ciliary localization of SMO. We propose that the disruption of transition-zone architecture in JBTS leads to a failure of SMO to accumulate at the transition zone and cilium, disrupting developmental signalling in JBTS.
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