CEP170B

CEP170B is a microtubule minus-end-binding protein that shapes a polarized microtubule network to establish cell polarity (PMID:37014312). It autonomously tracks growing microtubule minus ends and blocks their growth, and in complex with the kinesin KIF2A acts as a potent minus-end depolymerase that antagonizes the stabilizing activity of CAMSAP-family proteins (PMID:37014312). Its cortical deployment is scaffold-dependent: localization to cortical patches requires liprin-α1, and its microtubule-localizing activity requires liprin-α1-bound PP2A phosphatase, allowing cortical CEP170B to exclude CAMSAP-stabilized minus ends from the cell periphery and basal cortex and thereby support directional vesicle trafficking and 3D cyst formation (PMID:37014312). CEP170B also associates with the kinesin-13 depolymerase Kif2b through its C-terminus, providing an additional microtubule-binding context at the mitotic spindle (PMID:23087211).

1. 2012 Medium

   Before this work it was unclear how CEP170B engaged the microtubule cytoskeleton; the finding established a physical link to a kinesin-13 depolymerase and a microtubule-binding role.

   Evidence Co-immunoprecipitation/pulldown and in vitro microtubule-binding assay

   PMID:23087211

   Open questions at the time

   • single Co-IP/pulldown without reciprocal validation for CEP170B specifically
   • in vitro MT-binding was shown for Cep170, not fully resolved for CEP170B/KIAA0284
   • functional consequence of the Kif2b association at the spindle not directly tested
2. 2023 High

   It was unknown whether CEP170B had intrinsic minus-end activity; reconstitution showed it autonomously tracks and blocks MT minus ends and, with KIF2A, depolymerizes them to counter CAMSAP stabilization.

   Evidence In vitro reconstitution, live imaging, and loss-of-function assays in HeLa and human epithelial cells

   PMID:37014312

   Open questions at the time

   • structural basis of minus-end recognition not defined
   • how KIF2A and CEP170B are co-regulated at minus ends not established
3. 2023 High

   The mechanism of CEP170B cortical targeting was unknown; it was shown to depend on liprin-α1 and liprin-α1-bound PP2A, linking cortical positioning to exclusion of minus ends and to polarized trafficking and morphogenesis.

   Evidence Co-localization, knockdown/knockout with vesicle trafficking and 3D cyst formation readouts, and fractionation

   PMID:37014312

   Open questions at the time

   • PP2A substrate/dephosphorylation event controlling CEP170B localization not identified
   • molecular nature of the cortical patches not resolved

• How the spindle-associated Kif2b role and the cortical minus-end-exclusion role of CEP170B are integrated, and whether they operate in distinct cellular contexts, remains unresolved.
• no unified model linking mitotic and interphase functions
• regulation distinguishing KIF2A versus Kif2b partnerships unknown