Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells. / Song, Wenxin; Beigneux, Anne P.; Winther, Anne Marie L.; Kristensen, Kristian K.; Grønnemose, Anne L.; Yang, Ye; Tu, Yiping; Munguia, Priscilla; Morales, Jazmin; Jung, Hyesoo; De Jong, Pieter J.; Jung, Cris J.; Miyashita, Kazuya; Kimura, Takao; Nakajima, Katsuyuki; Murakami, Masami; Birrane, Gabriel; Jiang, Haibo; Tontonoz, Peter; Ploug, Michael; Fong, Loren G.; Young, Stephen G.

In: Journal of Clinical Investigation, Vol. 132, No. 5, e157500, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Song, W, Beigneux, AP, Winther, AML, Kristensen, KK, Grønnemose, AL, Yang, Y, Tu, Y, Munguia, P, Morales, J, Jung, H, De Jong, PJ, Jung, CJ, Miyashita, K, Kimura, T, Nakajima, K, Murakami, M, Birrane, G, Jiang, H, Tontonoz, P, Ploug, M, Fong, LG & Young, SG 2022, 'Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells', Journal of Clinical Investigation, vol. 132, no. 5, e157500. https://doi.org/10.1172/JCI157500

APA

Song, W., Beigneux, A. P., Winther, A. M. L., Kristensen, K. K., Grønnemose, A. L., Yang, Y., Tu, Y., Munguia, P., Morales, J., Jung, H., De Jong, P. J., Jung, C. J., Miyashita, K., Kimura, T., Nakajima, K., Murakami, M., Birrane, G., Jiang, H., Tontonoz, P., ... Young, S. G. (2022). Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells. Journal of Clinical Investigation, 132(5), [e157500]. https://doi.org/10.1172/JCI157500

Vancouver

Song W, Beigneux AP, Winther AML, Kristensen KK, Grønnemose AL, Yang Y et al. Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells. Journal of Clinical Investigation. 2022;132(5). e157500. https://doi.org/10.1172/JCI157500

Author

Song, Wenxin ; Beigneux, Anne P. ; Winther, Anne Marie L. ; Kristensen, Kristian K. ; Grønnemose, Anne L. ; Yang, Ye ; Tu, Yiping ; Munguia, Priscilla ; Morales, Jazmin ; Jung, Hyesoo ; De Jong, Pieter J. ; Jung, Cris J. ; Miyashita, Kazuya ; Kimura, Takao ; Nakajima, Katsuyuki ; Murakami, Masami ; Birrane, Gabriel ; Jiang, Haibo ; Tontonoz, Peter ; Ploug, Michael ; Fong, Loren G. ; Young, Stephen G. / Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells. In: Journal of Clinical Investigation. 2022 ; Vol. 132, No. 5.

Bibtex

@article{3a21707ef41d4444a0880a055ba228fb,
title = "Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells",
abstract = "GPIHBP1, an endothelial cell (EC) protein, captures lipoprotein lipase (LPL) within the interstitial spaces (where it is secreted by myocytes and adipocytes) and transports it across ECs to its site of action in the capillary lumen. GPIHBP1's 3-fingered LU domain is required for LPL binding, but the function of its acidic domain (AD) has remained unclear. We created mutant mice lacking the AD and found severe hypertriglyceridemia. As expected, the mutant GPIHBP1 retained the capacity to bind LPL. Unexpectedly, however, most of the GPIHBP1 and LPL in the mutant mice was located on the abluminal surface of ECs (explaining the hypertriglyceridemia). The GPIHBP1-bound LPL was trapped on the abluminal surface of ECs by electrostatic interactions between the large basic patch on the surface of LPL and negatively charged heparan sulfate proteoglycans (HSPGs) on the surface of ECs. GPIHBP1 trafficking across ECs in the mutant mice was normalized by disrupting LPL-HSPG electrostatic interactions with either heparin or an AD peptide. Thus, GPIHBP1's AD plays a crucial function in plasma triglyceride metabolism; it sheathes LPL's basic patch on the abluminal surface of ECs, thereby preventing LPL-HSPG interactions and freeing GPIHBP1-LPL complexes to move across ECs to the capillary lumen.",
author = "Wenxin Song and Beigneux, {Anne P.} and Winther, {Anne Marie L.} and Kristensen, {Kristian K.} and Gr{\o}nnemose, {Anne L.} and Ye Yang and Yiping Tu and Priscilla Munguia and Jazmin Morales and Hyesoo Jung and {De Jong}, {Pieter J.} and Jung, {Cris J.} and Kazuya Miyashita and Takao Kimura and Katsuyuki Nakajima and Masami Murakami and Gabriel Birrane and Haibo Jiang and Peter Tontonoz and Michael Ploug and Fong, {Loren G.} and Young, {Stephen G.}",
note = "Publisher Copyright: {\textcopyright} 2022 American Society for Clinical Investigation. All rights reserved.",
year = "2022",
doi = "10.1172/JCI157500",
language = "English",
volume = "132",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "American Society for Clinical Investigation",
number = "5",

}

RIS

TY - JOUR

T1 - Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells

AU - Song, Wenxin

AU - Beigneux, Anne P.

AU - Winther, Anne Marie L.

AU - Kristensen, Kristian K.

AU - Grønnemose, Anne L.

AU - Yang, Ye

AU - Tu, Yiping

AU - Munguia, Priscilla

AU - Morales, Jazmin

AU - Jung, Hyesoo

AU - De Jong, Pieter J.

AU - Jung, Cris J.

AU - Miyashita, Kazuya

AU - Kimura, Takao

AU - Nakajima, Katsuyuki

AU - Murakami, Masami

AU - Birrane, Gabriel

AU - Jiang, Haibo

AU - Tontonoz, Peter

AU - Ploug, Michael

AU - Fong, Loren G.

AU - Young, Stephen G.

N1 - Publisher Copyright: © 2022 American Society for Clinical Investigation. All rights reserved.

PY - 2022

Y1 - 2022

N2 - GPIHBP1, an endothelial cell (EC) protein, captures lipoprotein lipase (LPL) within the interstitial spaces (where it is secreted by myocytes and adipocytes) and transports it across ECs to its site of action in the capillary lumen. GPIHBP1's 3-fingered LU domain is required for LPL binding, but the function of its acidic domain (AD) has remained unclear. We created mutant mice lacking the AD and found severe hypertriglyceridemia. As expected, the mutant GPIHBP1 retained the capacity to bind LPL. Unexpectedly, however, most of the GPIHBP1 and LPL in the mutant mice was located on the abluminal surface of ECs (explaining the hypertriglyceridemia). The GPIHBP1-bound LPL was trapped on the abluminal surface of ECs by electrostatic interactions between the large basic patch on the surface of LPL and negatively charged heparan sulfate proteoglycans (HSPGs) on the surface of ECs. GPIHBP1 trafficking across ECs in the mutant mice was normalized by disrupting LPL-HSPG electrostatic interactions with either heparin or an AD peptide. Thus, GPIHBP1's AD plays a crucial function in plasma triglyceride metabolism; it sheathes LPL's basic patch on the abluminal surface of ECs, thereby preventing LPL-HSPG interactions and freeing GPIHBP1-LPL complexes to move across ECs to the capillary lumen.

AB - GPIHBP1, an endothelial cell (EC) protein, captures lipoprotein lipase (LPL) within the interstitial spaces (where it is secreted by myocytes and adipocytes) and transports it across ECs to its site of action in the capillary lumen. GPIHBP1's 3-fingered LU domain is required for LPL binding, but the function of its acidic domain (AD) has remained unclear. We created mutant mice lacking the AD and found severe hypertriglyceridemia. As expected, the mutant GPIHBP1 retained the capacity to bind LPL. Unexpectedly, however, most of the GPIHBP1 and LPL in the mutant mice was located on the abluminal surface of ECs (explaining the hypertriglyceridemia). The GPIHBP1-bound LPL was trapped on the abluminal surface of ECs by electrostatic interactions between the large basic patch on the surface of LPL and negatively charged heparan sulfate proteoglycans (HSPGs) on the surface of ECs. GPIHBP1 trafficking across ECs in the mutant mice was normalized by disrupting LPL-HSPG electrostatic interactions with either heparin or an AD peptide. Thus, GPIHBP1's AD plays a crucial function in plasma triglyceride metabolism; it sheathes LPL's basic patch on the abluminal surface of ECs, thereby preventing LPL-HSPG interactions and freeing GPIHBP1-LPL complexes to move across ECs to the capillary lumen.

U2 - 10.1172/JCI157500

DO - 10.1172/JCI157500

M3 - Journal article

C2 - 35229724

AN - SCOPUS:85125560699

VL - 132

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 5

M1 - e157500

ER -

ID: 300450482