CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium.

Abstract

Joubert syndrome (JS) is a developmental brain disorder characterized by cerebellar vermis hypoplasia, abnormal eye movement, ataxia and mental retardation. Mutations in CEP290 mutations are responsible for the cerebello-oculo-renal subtype of JS that includes kidney cysts and retinal degeneration, two phenotypes commonly linked to ciliopathies. CEP290 mutations are also associated with Meckel-Gruber syndrome and Bardet-Biedl syndrome (BBS). Here we demonstrate that CEP290 interacts with a centriolar satellite protein PCM-1, which is implicated in BBS4 function. CEP290 binds to PCM-1 and localizes to centriolar satellites in a PCM-1- and microtubule-dependent manner. The depletion of CEP290 disrupts subcellular distribution and protein complex formation of PCM-1. In accord with PCM-1's role in microtubule organization, CEP290 knockdown causes the disorganization of the cytoplasmic microtubule network. Moreover, we show that both CEP290 and PCM-1 are required for ciliogenesis and are involved in the ciliary targeting of Rab8, a small GTPase shown to collaborate with BBS protein complex to promote ciliogenesis. Our results suggest that PCM-1 is a potential mediator that may link CEP290 with BBS proteins in common molecular pathways.

• Authors: Joon Kim, Suguna Rani Krishnaswami, Joseph G Gleeson
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 17 Issue 23 Pg. 3796-805 (Dec 01 2008) ISSN: 1460-2083 [Electronic] England
• PMID: 18772192 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Autoantigens
• Cell Cycle Proteins
• Cep290 protein, human
• Cytoskeletal Proteins
• Neoplasm Proteins
• PCM1 protein, human
• RAB8A protein, human
• rab GTP-Binding Proteins

Topics

• Antigens, Neoplasm (genetics, metabolism)
• Autoantigens (genetics, metabolism)
• Brain Diseases (genetics, metabolism)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line
• Centrioles (genetics, metabolism)
• Cilia (genetics, metabolism)
• Cytoskeletal Proteins
• Humans
• Neoplasm Proteins (genetics, metabolism)
• Protein Binding
• Protein Transport
• rab GTP-Binding Proteins (genetics, metabolism)