science.org SCIENCEPHOTO: PAUL WHITTEN/SCIENCE SOURCE1318 10 DECEMBER 2021 • VOL 374 ISSUE 6573By Julie A. Brill1,2 and Andrew Wilde2,3D
efects in cytokinesis, the process
of cell separation at the end of the
cell division cycle, can lead to ane-
uploidy, genome instability, and ul-
timately, cancer ( 1 ). Accumulating
data also implicate cytokinesis de-
fects in various noncancer syndromes,
many of which present with neurological
or visual abnormalities. The recent discov-
ery that patients with oculoskeletodental
syndrome, caused by inactivating PIK3C2A(phosphatidylinositol-4-phosphate 3-kinase
catalytic subunit type 2a) mutations, de-
velop early-onset cataracts and secondary
glaucoma suggested that the encoded pro-
tein might normally function in cytokinesis
( 2 ). On page 1339 of this issue, Gulluni et al.
( 3 ) report that loss of PIK3C2A inhibits ab-
scission, the final stage of cytokinesis, and
triggers lens cell senescence and cataract
formation in zebrafish, mice, and humans.
PI3K-C2a, which is encoded by PIK3C2A,
is a phosphatidylinositol (PI) kinase that
modifies membrane lipids through phos-
phorylation. Individual PI phosphates
(PIPs) occur within the inner leaflet of cel-
lular membranes, where they form distinct
microdomains that recruit specific proteins
and thereby regulate diverse cellular pro-cesses. The best characterized PIP is phos-
phatidylinositol 4,5-bisphosphate [PI(4,5)
P 2 ], which, together with phosphatidylino-
sitol 4-phosphate [PI(4)P], establishes
plasma membrane identity; PIPs also bind
and facilitate the localization and activity of
transmembrane and peripheral proteins at
the plasma membrane ( 4 ). Dynamic remod-
eling of PIPs is a key regulatory mechanism,
and multiple studies confirm the impor-
tance of PIP remodeling during cytokinesis,
notably in the assembly and constriction of
the contractile ring that is required before
abscission ( 5 – 7 ).
Inhibition of cytokinesis leads to G 1 arrest
in the next cell cycle, followed by senescence
( 8 ). Gulluni et al. found that senescent mul-
tinucleated cells (resulting from defectiveCELL BIOLOGYA lipid primes the final cut in dividing cells
PERSPECTIVES
A newly described pathway activates separation of lens cells at the end of cytokinesis
INSIGHTS
(^1) Cell Biology Program, The Hospital for Sick Children,
Toronto, ON, Canada.^2 Department of Molecular Genetics,
University of Toronto, Toronto, ON, Canada.^3 Department of
Biochemistry, University of Toronto, Toronto, ON, Canada.
Email: [email protected]; [email protected]