HMMR/RHAMM recruits SACK1D/FAM83D-CK1α complex at the mitotic spindle to control spindle alignment

TL;DR

This paper reveals how HMMR helps assemble a complex at the mitotic spindle, ensuring proper cell division by stabilizing SACK1D and controlling its destruction.

Contribution

The study identifies HMMR's role in recruiting and stabilizing the SACK1D-CK1α complex at the mitotic spindle.

Findings

HMMR is essential for SACK1D-CK1α complex formation and spindle alignment.

HMMR stabilizes SACK1D by binding to its C-terminal α-helix.

Mitotic hyperphosphorylation of SACK1D signals its destruction after cell division.

Abstract

The SACK1D/FAM83D-CK1α complex assembles at the mitotic spindle to orchestrate proper spindle positioning and error-free progression through mitosis. The full molecular picture of how this complex assembles and disassembles over the cell division cycle remains to be fully defined. Here, we show that hyaluronan-mediated motility receptor (HMMR) is critical for SACK1D-CK1α complex formation at the spindle, co-localizes with the SACK1D-CK1α complex throughout mitosis, and is necessary for correct mitotic spindle alignment. We find that HMMR binds to the C-terminal α-helix of SACK1D, and this helix is also important for the mitotic interaction between SACK1D and CK1α. We demonstrate that HMMR binding stabilizes SACK1D. We map the mitotic hyperphosphorylation sites on SACK1D and show that this hyperphosphorylation signals the destruction of SACK1D upon mitotic exit. The destruction also requires the C-terminal α-helix of SACK1D, suggesting that hyperphosphorylation of SACK1D in mitosis potentially exposes the C-terminal degron sequences resident on SACK1D. This study provides key molecular insights into the assembly and fate of the HMMR-SACK1D-CK1α complex at the mitotic spindle.

•HMMR is required for CK1α mitotic spindle recruitment•The c-terminal α-helix of SACK1D is responsible for its association with HMMR•HMMR stabilizes SACK1D by binding its c-terminal α-helix•The c terminus and phosphorylation coordinate SACK1D post mitotic destruction

HMMR is required for CK1α mitotic spindle recruitment

The c-terminal α-helix of SACK1D is responsible for its association with HMMR

HMMR stabilizes SACK1D by binding its c-terminal α-helix

The c terminus and phosphorylation coordinate SACK1D post mitotic destruction

Cell biology; Molecular biology

Figures