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Updated: Apr 22, 2026

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
Published on: January 17, 2025
Farnesylated prelamin A induces fibroblast polarity defects in premature aging disorders by inhibiting nesprin-2-SUN2
Chonkit Lio1,2, Yuexia Wang3,4, Paige C Wilson5
1Faculty of Health Science, University of Macau, Taipa, Macau, China.
Abstract:
Disrupted processing of prelamin A (encoded by LMNA) causes Hutchinson-Gilford progeria syndrome (HGPS) and related premature aging disorders. The farnesylated prelamin A variant produced in HGPS, termed progerin, alters actin-nuclear interactions mediated by nesprin-2 and SUN2 linker of nucleoskeleton and cytoskeleton (LINC) complexes, resulting in defective cell polarization. To explore further how prelamin A causes these cellular defects, we examined other disease-causing variants that prevent cleavage of lamin A or reduce the activity of the processing enzyme ZMPSTE24. Accumulation of prelamin A or an uncleaved variant in cells reduced diffusional mobilities of nesprin-2 and SUN2 and inhibited their function in cell polarization in a farnesylation-dependent manner. Expression of short carboxyl-terminal tail fragments of prelamin A variants disrupted cell polarity in a farnesylation-dependent fashion. These results show that retention of the farnesyl moiety in the tails of prelamin A or its variants is the common element responsible for disrupting actin force transmission to the nucleus in premature aging syndromes and support the idea that altered function of actin-dependent LINC complexes is a critical component of premature aging.
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