CNTLN

Centlein (CNTLN) is a centriolar protein that maintains centrosome cohesion during interphase by acting as a molecular bridge within the proximal-end linker apparatus (PMID:24554434). It localizes to the proximal ends of centrioles and directly interacts with both C-Nap1 (Cep250) and Cep68, physically connecting the two; its depletion impairs recruitment of Cep68 to centrosomes and causes premature centrosome splitting (PMID:24554434). Centlein is a substrate of Nek2A kinase, placing the C-Nap1–centlein–Cep68 cohesion complex under phosphoregulatory control (PMID:24554434). Beyond these interactions and their regulation by Nek2A, no further mechanistic detail has been characterized in the available corpus.

1. 2014 High

   Established what molecular link holds centrioles together during interphase by identifying centlein as a direct bridge between C-Nap1 and Cep68 required for centrosome cohesion.

   Evidence Reciprocal Co-IP and direct interaction assays, immunofluorescence localization to centriole proximal ends, and siRNA depletion scored for centrosome splitting in human cells

   PMID:24554434

   Open questions at the time

   • Structural basis of the centlein–C-Nap1 and centlein–Cep68 interactions not resolved
   • Domains of centlein mediating each interaction not mapped
   • Single-lab study without independent replication
2. 2014 Medium

   Connected the cohesion linker to cell-cycle control by showing centlein (and Cep68) are phosphorylation substrates of Nek2A kinase.

   Evidence In vitro kinase assay identifying centlein and Cep68 as novel Nek2A substrates

   PMID:24554434

   Open questions at the time

   • Phosphorylation sites and functional mutagenesis not characterized in the report
   • Whether Nek2A phosphorylation disassembles the cohesion complex in cells is untested
   • No in vivo confirmation of the phosphorylation event

• How Nek2A phosphorylation of centlein is coupled to the timing of centrosome separation at mitotic entry remains unresolved.
• No phosphosite-level mechanism linking centlein modification to linker dissolution
• No structural model of the C-Nap1–centlein–Cep68 bridge