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PMID:26766442

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Citation

Chiu, CWN, Monat, C, Robitaille, M, Lacomme, M, Daulat, AM, Macleod, G, McNeill, H, Cayouette, M and Angers, S (2016) SAPCD2 Controls Spindle Orientation and Asymmetric Divisions by Negatively Regulating the Gαi-LGN-NuMA Ternary Complex. Dev. Cell 36:50-62

Abstract

Control of cell-division orientation is integral to epithelial morphogenesis and asymmetric cell division. Proper spatiotemporal localization of the evolutionarily conserved Gαi-LGN-NuMA protein complex is critical for mitotic spindle orientation, but how this is achieved remains unclear. Here we identify Suppressor APC domain containing 2 (SAPCD2) as a previously unreported LGN-interacting protein. We show that SAPCD2 is essential to instruct planar mitotic spindle orientation in both epithelial cell cultures and mouse retinal progenitor cells in vivo. Loss of SAPCD2 randomizes spindle orientation, which in turn disrupts cyst morphogenesis in three-dimensional cultures, and triples the number of terminal asymmetric cell divisions in the developing retina. Mechanistically, we show that SAPCD2 negatively regulates the localization of LGN at the cell cortex, likely by competing with NuMA for its binding. These results uncover SAPCD2 as a key regulator of the ternary complex controlling spindle orientation during morphogenesis and asymmetric cell divisions.

Links

PubMed Online version:10.1016/j.devcel.2015.12.016

Keywords

Animals; Antigens, Nuclear/metabolism; Cell Cycle/genetics; Cell Polarity/genetics; Cell Polarity/physiology; Humans; Mice; Mitosis/physiology; Morphogenesis/physiology; Nuclear Matrix-Associated Proteins/metabolism; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Protein Binding; Spindle Apparatus/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:NUMA1

located_in

GO:0097575: lateral cell cortex

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:GNAI1

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:GNAI1

involved_in

GO:1904778: positive regulation of protein localization to cell cortex

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GPSM2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q86UD0

F

Seeded From UniProt

complete

HUMAN:GPSM2

located_in

GO:0097575: lateral cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SAPC2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8TEW0

F

Seeded From UniProt

complete

HUMAN:SAPC2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P81274

F

Seeded From UniProt

complete

HUMAN:SAPC2

located_in

GO:0043296: apical junction complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SAPC2

located_in

GO:0045179: apical cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SAPC2

involved_in

GO:1904777: negative regulation of protein localization to cell cortex

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PARD3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q86UD0

F

Seeded From UniProt

complete

MOUSE:GPSM2

located_in

GO:0097575: lateral cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SAPC2

involved_in

GO:0000132: establishment of mitotic spindle orientation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SAPC2

located_in

GO:0045179: apical cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SAPC2

involved_in

GO:0098725: symmetric cell division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SAPC2

involved_in

GO:0090175: regulation of establishment of planar polarity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GPSM2

part_of

GO:0097575: lateral cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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