CXCL12 secretion by bone marrow stromal cells is dependent on cell contact and mediated by connexin-43 and connexin-45 gap junctions View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-05

AUTHORS

Amir Schajnovitz, Tomer Itkin, Gabriele D'Uva, Alexander Kalinkovich, Karin Golan, Aya Ludin, Dror Cohen, Ziv Shulman, Abraham Avigdor, Arnon Nagler, Orit Kollet, Rony Seger, Tsvee Lapidot

ABSTRACT

The chemokine CXCL12 is essential for the function of hematopoietic stem and progenitor cells. Here we report that secretion of functional CXCL12 from human bone marrow stromal cells (BMSCs) was a cell contact-dependent event mediated by connexin-43 (Cx43) and Cx45 gap junctions. Inhibition of connexin gap junctions impaired the secretion of CXCL12 and homing of leukocytes to mouse bone marrow. Purified human CD34(+) progenitor cells did not adhere to noncontacting BMSCs, which led to a much smaller pool of immature cells. Calcium conduction activated signaling by cAMP-protein kinase A (PKA) and induced CXCL12 secretion mediated by the GTPase RalA. Cx43 and Cx45 additionally controlled Cxcl12 transcription by regulating the nuclear localization of the transcription factor Sp1. We suggest that BMSCs form a dynamic syncytium via connexin gap junctions that regulates CXC12 secretion and the homeostasis of hematopoietic stem cells. More... »

PAGES

391

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ni.2017

DOI

http://dx.doi.org/10.1038/ni.2017

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1041406954

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21441933


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