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

TY - JOUR

T1 - HMMR/RHAMM recruits SACK1D/FAM83D-CK1α complex at the mitotic spindle to control spindle alignment

AU - Cartwright, Tyrell N.

AU - Nakarakanti, Naveen K.

AU - Dunbar, Karen

AU - Fulcher, Luke J.

AU - Bader, Selina

AU - Wood, Nicola T.

AU - Macartney, Thomas J.

AU - Sapkota, Gopal

N1 - © 2025

PY - 2025/12/12

Y1 - 2025/12/12

N2 - 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 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.

AB - 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 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.

U2 - 10.1016/j.isci.2025.114417

DO - 10.1016/j.isci.2025.114417

M3 - Article

SN - 2589-0042

VL - 29

JO - iScience

JF - iScience

IS - 1

M1 - 114417

ER -