KATNBL1

KATNBL1 is a regulatory B-like subunit of the katanin microtubule-severing machinery that controls the catalytic A subunits KATNA1 and KATNAL1 (PMID:26929214). It physically associates with both A subunits and directly modulates their microtubule-severing activity in vitro (PMID:26929214). KATNBL1 displays cell-cycle-dependent localization: an N-terminal nuclear localization signal sequesters it in the nucleus during interphase, and it relocates to spindle poles during mitosis, coupling its regulatory action to specific cell-cycle stages (PMID:26929214). The canonical B subunit KATNB1 competes with KATNBL1 for binding to KATNA1 and KATNAL1, indicating that the two B-type subunits coordinately tune katanin activity (PMID:26929214). Beyond these interaction, localization, and severing-regulation findings, no further mechanistic detail has been characterized in the available corpus.

1. 2016 Medium

   Establishing the physical partners of KATNBL1 was needed to place it within the katanin system; proteomic mapping showed it associates with the catalytic A subunits KATNA1 and KATNAL1.

   Evidence Mass spectrometry interactome and co-immunoprecipitation in the Katan-ome network

   PMID:26929214

   Open questions at the time

   • Binding interface and stoichiometry with KATNA1/KATNAL1 not defined
   • No reciprocal validation across independent labs
2. 2016 High

   Whether KATNBL1 functionally affects katanin catalysis, not merely binds it, was open; an in vitro severing assay showed it regulates KATNA1 and KATNAL1 microtubule-severing activity.

   Evidence Reconstituted in vitro microtubule-severing assay with defined A subunits

   PMID:26929214

   Open questions at the time

   • Direction and magnitude of regulation (activation vs inhibition) not detailed here
   • Structural basis of the regulatory effect unknown
3. 2016 Medium

   How KATNBL1 activity is spatially and temporally restricted was unknown; imaging revealed NLS-mediated nuclear sequestration in interphase and relocation to spindle poles in mitosis.

   Evidence Fluorescence subcellular localization with NLS identification and functional localization experiments

   PMID:26929214

   Open questions at the time

   • Mechanism and regulation of mitotic relocation to spindle poles unknown
   • Functional consequence of nuclear sequestration not established
4. 2016 Medium

   Whether the two B-type subunits act independently or competitively was unresolved; competition binding showed KATNB1 displaces KATNBL1 from KATNA1 and KATNAL1.

   Evidence Co-immunoprecipitation competition assay

   PMID:26929214

   Open questions at the time

   • Quantitative affinities and physiological balance between KATNB1 and KATNBL1 not measured
   • Functional outcome of competition on severing activity in cells not shown

• The direction of KATNBL1's regulatory effect on severing, the structural basis of A-subunit binding, and the in vivo consequences of its nuclear-to-spindle-pole shuttling remain unresolved.
• No structural model of the KATNBL1–A subunit interaction
• In vivo phenotype of KATNBL1 loss not characterized in the corpus
• Regulatory mechanism of cell-cycle-dependent relocalization unknown