LRRK1

Cilia effects upon perturbation of LRRK1

Loss-of-function effect:

Incrased cilia number

Phenotypes

Mouse phenotype:

abnormal locomotor behavior; abnormal rib morphology; absent teeth; abnormal humerus morphology; abnormal radius morphology; abnormal eyelid morphology; abnormal tooth morphology; increased red blood cell distribution width; decreased lean body mass; abnormal ulna morphology; increased bone mineral content; increased neutrophil cell number; decreased lymphocyte cell number; abnormal snout morphology; abnormal gait; increased circulating iron level; decreased eosinophil cell number; abnormal pelvic girdle bone morphology; abnormal zygomatic bone morphology; abnormal femur morphology; increased circulating cholesterol level; increased bone mineral density; thrombocytopenia; abnormal fibula morphology; increased spleen weight; abnormal maxilla morphology; abnormal clavicle morphology; abnormal bone structure; abnormal tibia morphology; abnormal mandible morphology; increased circulating HDL cholesterol level; increased total body fat amount; increased circulating phosphate level; decreased leukocyte cell number; increased circulating creatine kinase level; abnormal vertebrae morphology; decreased circulating alkaline phosphatase level; abnormal joint morphology

Mouse ciliopathy phenotype:

increased circulating aspartate transaminase level; short tibia

Subcellular localization

basal body

Functional category

• Motors (dynein/kinesin)
• Ciliary assembly/disassembly

Function

The depletion of LRRK1 impairs primary cilia resorption following serum stimulation in cultured cells. Polo-like kinase 1 (PLK1) plays an important role in this process. During ciliary resorption, PLK1 phosphorylates LRRK1 at the primary cilia base, resulting in its activation. We identified nuclear distribution protein nudE-like 1 (NDEL1), which is known to positively regulate cilia disassembly, as a target of LRRK1 phosphorylation. Whereas LRRK1 phosphorylation of NDEL1 on Ser-155 promotes NDEL1 interaction with the intermediate chains of cytoplasmic dynein-2, it is also crucial for triggering ciliary resorption through dynein-2-driven retrograde intraflagellar transport. These findings provide evidence that a novel PLK1-LRRK1-NDEL1 pathway regulates cilia disassembly(36254578).