HAUS8

HAUS8 (Hice1) is a microtubule-associated subunit of the augmin complex that drives microtubule-based microtubule nucleation during bipolar spindle assembly (PMID:18362163, PMID:41173848). Its disordered N-terminal region directly binds, bundles, and stabilizes microtubules and constitutes a second MT-binding site within augmin (alongside the Haus6 CH domain), where it contributes to MT affinity and establishes the shallow branch angle characteristic of branching nucleation (PMID:18362163, PMID:41173848). Augmin engagement with microtubules is spatially gated by the Ran system: importin-α/β bind NLS sequences on HAUS8 that overlap its MT-binding site, blocking MT interaction until RanGTP releases the inhibition near chromosomes (PMID:37086784, PMID:37357828). This activity is further tuned by mitotic kinases—Aurora-A phosphorylates an N-terminal Ser/Thr-17-21 cluster to reduce MT binding and spindle localization, while Plk1 phosphorylation promotes the augmin-MT interaction and γ-tubulin recruitment to spindles (PMID:21705324, PMID:21690413). HAUS8 also interacts with Hec1 through its first coiled-coil domain to support centrosome-directed microtubule growth, and contributes to spindle poleward flux and chromosome alignment fidelity (PMID:19776357, PMID:39541344). Depletion produces unstable spindles, mitotic delay, and aneuploidy (PMID:18362163). Beyond its mitotic role, HAUS8 has been reported as a positive regulator of RIG-I/MAVS antiviral signaling (PMID:29916539).

1. 2008 High

   Established HAUS8 as a microtubule-associated protein with intrinsic MT-binding activity and a mitotic spindle function, answering whether the protein acts directly on microtubules.

   Evidence RNAi depletion with spindle phenotyping plus in vitro MT bundling/stabilization with recombinant N-terminal fragments

   PMID:18362163

   Open questions at the time

   • Did not place HAUS8 within the augmin complex
   • Mechanism of spindle recruitment unknown
2. 2009 High

   Identified a direct Hice1-Hec1 interaction required for centrosome-directed MT growth, linking HAUS8 to centrosomal nucleation.

   Evidence Co-IP, domain-mapped binding via coiled-coil 1, in vitro centrosome aster assay with antibody neutralization and deletion-mutant rescue

   PMID:19776357

   Open questions at the time

   • Structural basis of the coiled-coil interaction not resolved
   • Relationship to augmin-dependent branching nucleation not addressed
3. 2011 High

   Showed that Aurora-A and Plk1 phosphorylation tune HAUS8 MT-binding and augmin recruitment, establishing kinase control over branching nucleation timing.

   Evidence In vitro kinase assays, phospho-specific antibodies, phospho-mimic/deficient mutants in MT binding and spindle localization, MT co-sedimentation and γ-tubulin recruitment readouts

   PMID:21690413 PMID:21705324

   Open questions at the time

   • Interplay between Aurora-A and Plk1 inputs not integrated
   • Quantitative contribution of each phospho-site to spindle assembly in vivo unclear
4. 2023 High

   Defined the Ran-GTP/importin mechanism that spatially restricts augmin MT binding via NLS sequences on HAUS8, explaining how branching nucleation is targeted near chromosomes.

   Evidence In vitro pulldowns, TIRF microscopy, NLS mapping on Haus8, and Xenopus egg extract validation; independently replicated

   PMID:37086784 PMID:37357828

   Open questions at the time

   • Crosstalk between importin gating and kinase phosphorylation not resolved
   • In-cell quantification of the RanGTP gradient effect on HAUS8 limited
5. 2025 High

   Provided structural evidence that the disordered HAUS8 N-terminus forms a second MT-binding site shaping the augmin branch angle, defining its mechanical role in branching geometry.

   Evidence Cryo-EM of an augmin subcomplex on microtubules with domain mutagenesis and branching nucleation assays

   PMID:41173848

   Open questions at the time

   • Full-complex structure with all subunits not resolved
   • How phosphorylation and importin binding alter this interface structurally unknown
6. 2024 Medium

   Positioned HAUS8 as a contributor to spindle poleward flux and chromosome alignment through epistasis with KIF18A.

   Evidence siRNA co-depletion rescue in RPE-1 cells with live-cell and speckle microscopy measuring MT overlap and flux

   PMID:39541344

   Open questions at the time

   • Direct molecular link between HAUS8 and flux machinery not established
   • Single-study epistasis without reconstitution
7. 2018 Medium

   Reported a non-mitotic role for HAUS8 as a positive regulator of RIG-I/MAVS antiviral innate immune signaling.

   Evidence Co-IP with VISA/RIG-I/TBK1, overexpression/knockdown, luciferase reporters, and ubiquitination assays after Sendai virus infection

   PMID:29916539

   Open questions at the time

   • Single lab, no structural or reconstitution validation
   • Mechanism linking augmin function to antiviral signaling unexplained
   • Role unexpected given canonical spindle function

• How importin gating, Aurora-A/Plk1 phosphorylation, and the structural MT-binding interface are integrated into a single regulated nucleation event remains unresolved.
• No unified model coordinating spatial (Ran) and temporal (kinase) control
• Reconciliation of mitotic and antiviral functions absent