Your browser doesn't support javascript.
loading
Progerin forms an abnormal meshwork and has a dominant-negative effect on the nuclear lamina.
Kim, Paul H; Kim, Joonyoung R; Tu, Yiping; Jung, Hyesoo; Jeong, J Y Brian; Tran, Anh P; Presnell, Ashley; Young, Stephen G; Fong, Loren G.
Afiliación
  • Kim PH; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
  • Kim JR; Department of Bioengineering, University of California, Los Angeles, CA 90095.
  • Tu Y; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
  • Jung H; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
  • Jeong JYB; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
  • Tran AP; Advanced Light Microscopy and Spectroscopy Laboratory, California NanoSystems Institute, University of California, Los Angeles, CA 90095.
  • Presnell A; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
  • Young SG; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
  • Fong LG; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Proc Natl Acad Sci U S A ; 121(27): e2406946121, 2024 Jul 02.
Article en En | MEDLINE | ID: mdl-38917015
ABSTRACT
Progerin, the protein that causes Hutchinson-Gilford progeria syndrome, triggers nuclear membrane (NM) ruptures and blebs, but the mechanisms are unclear. We suspected that the expression of progerin changes the overall structure of the nuclear lamina. High-resolution microscopy of smooth muscle cells (SMCs) revealed that lamin A and lamin B1 form independent meshworks with uniformly spaced openings (~0.085 µm2). The expression of progerin in SMCs resulted in the formation of an irregular meshwork with clusters of large openings (up to 1.4 µm2). The expression of progerin acted in a dominant-negative fashion to disrupt the morphology of the endogenous lamin B1 meshwork, triggering irregularities and large openings that closely resembled the irregularities and openings in the progerin meshwork. These abnormal meshworks were strongly associated with NM ruptures and blebs. Of note, the progerin meshwork was markedly abnormal in nuclear blebs that were deficient in lamin B1 (~50% of all blebs). That observation suggested that higher levels of lamin B1 expression might normalize the progerin meshwork and prevent NM ruptures and blebs. Indeed, increased lamin B1 expression reversed the morphological abnormalities in the progerin meshwork and markedly reduced the frequency of NM ruptures and blebs. Thus, progerin expression disrupts the overall structure of the nuclear lamina, but that effect-along with NM ruptures and blebs-can be abrogated by increased lamin B1 expression.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lámina Nuclear / Lamina Tipo A / Lamina Tipo B Límite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lámina Nuclear / Lamina Tipo A / Lamina Tipo B Límite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos