PXD077779

PXD077779 is an original dataset announced via ProteomeXchange.

Title	Excess muscle plasma membrane leak disrupts extracellular matrix content and shifts macrophage-mediated muscle repair
Description	Plasma membrane repair is critical for tissue integrity, especially for elongated contractile muscle cells. Genetically-mediated defects in plasma membrane resealing produce persistent leak, leading to a disordered extracellular matrix. Loss of the membrane repair protein dysferlin slows sarcolemmal resealing and promotes excess leak. Annexin A6 is also implicated in sarcolemmal repair, forming repair caps at the site of membrane disruption. On its own, deletion of the gene for annexin A6, Anxa6, had little effect on muscle health. In contrast, combined loss of dysferlin and annexin A6 (DysfA6) generated muscle fibers with profoundly defective membrane leak. Strikingly, Anxa6 deletion in the context of loss of dystrophin (mdxA6) did not exacerbate muscle defects. The persistent membrane leak in DysfA6 muscle resulted in marked macrophage infiltration with disordered macrophage polarization. Injured muscle fibers were targets of macrophage efferocytosis. Loss of Anxa6 was associated with increased expression of annexins A1 and A2, both of which were heavily deposited into the extracellular matrix. In vitro, macrophages exposed to annexins A1 and A2 expressed increased Csf1, consistent with a model where excess leak results in annexins A1 and A2 in the extracellular matrix, where this protein composition elicits macrophage proliferation and efferocytosis.
HostingRepository	PRIDE
AnnounceDate	2026-06-15
AnnouncementXML	Submission_2026-06-15_15:24:10.258.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kirk Hansen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	2-pyrrolidone-5-carboxylic acid (Gln); acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-29 00:16:38	ID requested
⏵ 1	2026-06-15 15:24:10	announced

Dataset with its publication pending

submitter keyword: macrophage, muscle injury,Dysferlin, Duchenne muscular dystrophy, Limb Girdle muscular dystrophy, annexin, extracellular matrix

Alexis Demonbreun
contact affiliation	Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
contact email	alexis.demonbreun@northwestern.edu
lab head
Kirk Hansen
contact affiliation	Univeristy of Colorado
contact email	kirk.hansen@cuanschutz.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD077779
     1. Label: PRIDE project
     2. Name: Excess muscle plasma membrane leak disrupts extracellular matrix content and shifts macrophage-mediated muscle repair