INPP5E interacts with AURKA, linking phosphoinositide signaling to primary cilium stability.
Mutations in inositol polyphosphate 5-phosphatase E (INPP5E) cause the ciliopathies known as Joubert and MORM syndromes; however, the role of INPP5E in ciliary biology is not well understood. Here, we describe an interaction between INPP5E and AURKA, a centrosomal kinase that regulates mitosis and ciliary disassembly, and we show that this interaction is important for the stability of primary cilia. Furthermore, AURKA phosphorylates INPP5E and thereby increases its 5-phosphatase activity, which in turn promotes transcriptional downregulation of AURKA, partly through an AKT-dependent mechanism. These findings establish the first direct link between AURKA and phosphoinositide signaling and suggest that the function of INPP5E in cilia is at least partly mediated by its interactions with AURKA.
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Olga V
OV
Plotnikova
Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242.
Seongjin
S
Seo
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Denny L
DL
Cottle
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Sarah
S
Conduit
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Sandra
S
Hakim
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Jennifer M
JM
Dyson
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Christina A
CA
Mitchell
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia ian.smyth@monash.edu.
Ian M
IM
Smyth
D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000002:abnormalities / Q000473:pathology; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D005124:Eye Abnormalities / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics / Q000473:pathology; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D060066:Protein Interaction Maps / Q000235:genetics; D012160:Retina / Q000002:abnormalities / Q000473:pathology; D015398:Signal Transduction; D000099182:Phosphoinositide 5-Phosphatases
D064096:Aurora Kinase A; D010716:Phosphatidylinositols; D010744:Phosphoric Monoester Hydrolases; D000099182:Phosphoinositide 5-Phosphatases; C576917:AURKA protein, human
AURKA; INPP5E; Primary cilium