The lipoprotein lipase that is shuttled into capillaries by GPIHBP1 enters the glycocalyx where it mediates lipoprotein processing

Wenxin Song, Anne P. Beigneux, Thomas A. Weston, Kai Chen, Ye Yang, Le Phuong Nguyen, Paul Guagliardo, Hyesoo Jung, Anh P. Tran, Yiping Tu, Caitlyn Tran, Gabriel Birrane, Kazuya Miyashita, Katsuyuki Nakajima, Masami Murakami, Peter Tontonoz, Haibo Jiang, Michael Ploug, Loren G. Fong, Stephen G. Young

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Lipoprotein lipase (LPL), the enzyme that carries out the lipolytic processing of triglyceride-rich lipoproteins (TRLs), is synthesized by adipocytes and myocytes and secreted into the interstitial spaces. The LPL is then bound by GPIHBP1, a GPI-anchored protein of endothelial cells (ECs), and transported across ECs to the capillary lumen. The assumption has been that the LPL that is moved into capillaries remains attached to GPIHBP1 and that GPIHBP1 serves as a platform for TRL processing. In the current studies, we examined the validity of that assumption. We found that an LPL-specific monoclonal antibody (mAb), 88B8, which lacks the ability to detect GPIHBP1-bound LPL, binds avidly to LPL within capillaries. We further demonstrated, by confocal microscopy, immunogold electron microscopy, and nanoscale secondary ion mass spectrometry analyses, that the LPL detected by mAb 88B8 is located within the EC glycocalyx, distant from the GPIHBP1 on the EC plasma membrane. The LPL within the glycocalyx mediates the margination of TRLs along capillaries and is active in TRL processing, resulting in the delivery of lipoprotein-derived lipids to immediately adjacent parenchymal cells. Thus, the LPL that GPIHBP1 transports into capillaries can detach and move into the EC glycocalyx, where it functions in the intravascular processing of TRLs.

Original languageEnglish
Pages (from-to)e2313825120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number44
DOIs
Publication statusPublished - 31 Oct 2023

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