Data from paper: Palmdelphin Regulates Nuclear Resilience to Mechanical Stress in the Endothelium
type: Dataset
description: Raw data from bulk RNA-Seq on endothelial cell cultures grown under static or laminar flow conditions after silencing Palmdelphin or not. Paper abstract: Background: Palmdelphin (PALMD), a protein of unknown function, belongs to the family of Paralemmin proteins implicated in cytoskeletal regulation. Single nucleotide polymorphisms (SNPs) in the PALMD locus, which reduce its expression, are strong risk factors for development of calcific aortic valve stenosis (CAVS) and for severity of the disease. Methods: Public database screening and immunodetection of PALMD showed dominant expression in endothelial cells (ECs). Mass spectrometry allowed identification of PALMD partners. The consequence of loss of PALMD expression was assessed in siRNA silenced EC cultures, in knockout mice and in human valve samples and EC cultures from patients. RNA sequencing on siRNA silenced cells and transcript arrays on valve samples from a Swedish SNP rs7543130 patient cohort informed about gene regulatory changes. Results: ECs express the cytoplasmic PALMD-KKVI splice variant, which was shown to exist in complex with RAN GTPase activating protein1 (RANGAP1). RANGAP1 regulates the activity of the GTPase RAN and thereby, nucleocytoplasmic shuttling via Exportin1 (XPO1). Reduced PALMD expression resulted in subcellular relocalization of RANGAP1 and XPO1, providing a mechanism for the gene regulatory changes established in PALMD-deficiency. Gene ontology analysis showed enrichment of actin and RHO GTPAse related terms in PALMD-silenced ECs. In accordance, PALMD-silenced ECs showed multiple changes in adhesive and migratory properties and cells were softer. In particular, PALMD-deficient ECs failed to form a perinuclear actin cap when exposed to flow. The perinuclear actin cap is known to provide protection against mechanical stress. Lack of the actin cap correlated with tilting of the nuclear long axis relative to the cell body, which was established in PALMD-deficient ECs, mice and patient …
conditions of access: https://publications.europa.eu/resource/authority/access-right/NON_PUBLIC
conditions of access: info:eu-repo/semantics/restrictedAccess
creative work status: completed
  type: DefinedTerm
  in defined term set: http://publications.europa.eu/resource/authority/dataset-status
  term code: COMPLETED
creator: Lena Claesson-Welsh
  type: Person
  affiliation: Science for Life Laboratory
  family name: Claesson-Welsh
  given name: Lena
creator: Miguel Sainz Jaspeado
  type: Person
  affiliation: Science for Life Laboratory
  family name: Sainz Jaspeado
  given name: Miguel
date modified: 2023-05-31
date published: 2021-11-01
keywords: Medical and Health Sciences
  type: DefinedTerm
  term code: 3
keywords: Cardiology and Cardiovascular Disease
  type: DefinedTerm
  term code: 30206
keywords: Cardiology (incl. cardiovascular diseases)
publisher: Uppsala University
version: 0

PropertyValue
property ID: DOI
value: 10.17044/SCILIFELAB.14270159

Science for Life Laboratory
type: Organization

Uppsala University
type: Organization