Page 84 - ebook

[B. Cell Biology/Stem Cell] B-42

Cytoskeletal tension dependent progression of nuclear

deformation in progerin expressing cells

Juhyeon Jo¹, Dong-Hwee Kim¹,²*

¹KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea,

²Department of Integrative Energy Engineering, College of Engineering, Korea University, Seoul 02841, Korea

The cell nucleus is wrapped by nuclear lamina consisting of A- and B-type lamin proteins under nuclear envelope

(NE). Recent studies have shown mutations in the LMNA encoding lamin A and C cause numerous genetic disorders.
In particular, the Hutchinson-Gilford progeria syndrome (HGPS) featuring premature aging disease caused by a

mutation in the LMNA gene, leading to increased production of truncated prelamin A, progerin. As the HGPS
patients display accumulated progerin at the nuclear membrane (NM) that results in abnormal nuclear morphology.

While the NE is a mechano-responsive element that plays a critical role in regulation of mechanical signal
transduction conveyed from extracellular microenvironment, however, how the molecular mechanism of progerin

accumulation dependent nuclear deformation remains unclear. Here we present a time-lapse nuclear deformation
monitoring via a doxycycline-controlled progerin inducible Hela cell by the Tet-On system. Furthermore, by using

nesprin tension sensor, we monitor that progerin expression leads to nuclear deformation in response to alteration
of myosin-dependent nuclear tension. We expect that the progerin-inducible Tet-On system will provide a new

approach to investigate how the progerin expression alter the nucleus and cytoskeletal connection, which is critical
to find important role of the nuclear lamina mediating mechanotransduction in biological aging process.