N-BAR and F-BAR proteins-endophilin-A3 and PSTPIP1-control clathrin-independent endocytosis of L1CAM

Camille Lemaigre; Apolline Ceuppens; Cesar Augusto Valades-Cruz; Benjamin Ledoux; Bastien Vanbeneden; Mujtaba Hassan; Fredrik R Zetterberg; Ulf J Nilsson; Ludger Johannes; Christian Wunder; Henri-François Renard; Pierre Morsomme

doi:10.1111/tra.12883

N-BAR and F-BAR proteins-endophilin-A3 and PSTPIP1-control clathrin-independent endocytosis of L1CAM

Camille Lemaigre
, Apolline Ceuppens
, Cesar Augusto Valades-Cruz
, Benjamin Ledoux
, Bastien Vanbeneden
, Mujtaba Hassan
, Fredrik R Zetterberg
, Ulf J Nilsson
, Ludger Johannes
, Christian Wunder
, Henri-François Renard
, Pierre Morsomme

Research output: Contribution to journal › Article › peer-review

Abstract

Recent advances in the field demonstrate the high diversity and complexity of endocytic pathways. In the current study, we focus on the endocytosis of L1CAM. This glycoprotein plays a major role in the development of the nervous system, and is involved in cancer development and is associated with metastases and poor prognosis. Two L1CAM isoforms are subject to endocytosis: isoform 1, described as a clathrin-mediated cargo; isoform 2, whose endocytosis has never been studied. Deciphering the molecular machinery of isoform 2 internalisation should contribute to a better understanding of its pathophysiological role. First, we demonstrated in our cellular context that both isoforms of L1CAM are mainly a clathrin-independent cargo, which was not expected for isoform 1. Second, the mechanism of L1CAM endocytosis is specifically mediated by the N-BAR domain protein endophilin-A3. Third, we discovered PSTPIP1, an F-BAR domain protein, as a novel actor in this endocytic process. Finally, we identified galectins as endocytic partners and negative regulators of L1CAM endocytosis. In summary, the interplay of the BAR proteins endophilin-A3 and PSTPIP1, and galectins fine tune the clathrin-independent endocytosis of L1CAM.

Original language	English
Pages (from-to)	190-212
Number of pages	23
Journal	Traffic
Volume	24
Issue number	4
DOIs	https://doi.org/10.1111/tra.12883
Publication status	Published - Apr 2023
Externally published	Yes

Funding

We would like to acknowledge the following people for help in experiments and expertise or providing materials: F. Tyckaert, H. Leffler, D. Durbin and E. Smythe. We thank B. Knoops, P. Dumont and F. Gofflot from LIBST (UCLouvain) for sharing cell culture and flow cytometry facilities and materials. We thank C. Bugli for help concerning statistical analysis. We acknowledge the following imaging core facilities: IMABIOL (LIBST, UCLouvain) and Morph-Im (UNamur). We thank D. Brusa and the Flow Cytometry platform of IREC (UCLouvain). We also would like to acknowledge the Cell and Tissue Imaging Platform (PICT-IBiSA) of the Curie Institute, member of the national infrastructure France-BioImaging and L. Leconte for technical assistance during LLSM acquisitions. Pierre Morsomme is supported by grants from the “Fonds National de la Recherche Scientifique” (FNRS, CDR-J.0119.19) and the “Communauté française de Belgique–Actions de Recherches Concertées” (17/22-085). Henri-François Renard is supported by a Start-Up Grant Collen-Francqui from Francqui Foundation and an Incentive Grant for Scientific Research from the “Fonds de la Recherche Scientifique” (FNRS, MIS-F.4540.21). Camille Lemaigre and Benjamin Ledoux are supported by PhD fellowships from FRIA/FNRS (Belgium). This work was also supported by the France BioImaging Infrastructure (French National Research Agency, ANR-10 INBS-04-07, “Investments for the future”), the Labex DCBiol (ANR-11-LABX-0043) and the Labex Cell(n)Scale (ANR-11-LABX-0038) as part of the Idex PSL (ANR-10-IDEX-0001-02). Agence Nationale de la Recherche; Fédération Wallonie‐Bruxelles; Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture; Fonds National de la Recherche Scientifique, Grant/Award Number: CDR‐J.0119.19; Communauté française de Belgique–Actions de Recherches Concertées, Grant/Award Number: 17/22‐085; Fonds de La Recherche Scientifique ‐ FNRS, Grant/Award Number: MIS‐F.4540.21; French National Research Agency, Grant/Award Number: ANR‐10 INBS‐04‐07; Labex DCBiol, Grant/Award Number: ANR‐11‐LABX‐0043; Labex Cell(n)Scale, Grant/Award Number: ANR‐11‐LABX‐0038; Idex PSL, Grant/Award Number: ANR‐10‐IDEX‐0001‐02 Funding information We would like to acknowledge the following people for help in experiments and expertise or providing materials: F. Tyckaert, H. Leffler, D. Durbin and E. Smythe. We thank B. Knoops, P. Dumont and F. Gofflot from LIBST (UCLouvain) for sharing cell culture and flow cytometry facilities and materials. We thank C. Bugli for help concerning statistical analysis. We acknowledge the following imaging core facilities: IMABIOL (LIBST, UCLouvain) and Morph‐Im (UNamur). We thank D. Brusa and the Flow Cytometry platform of IREC (UCLouvain). We also would like to acknowledge the Cell and Tissue Imaging Platform (PICT‐IBiSA) of the Curie Institute, member of the national infrastructure France‐BioImaging and L. Leconte for technical assistance during LLSM acquisitions. Pierre Morsomme is supported by grants from the “Fonds National de la Recherche Scientifique” (FNRS, CDR‐J.0119.19) and the “Communauté française de Belgique–Actions de Recherches Concertées” (17/22‐085). Henri‐François Renard is supported by a Start‐Up Grant Collen‐Francqui from Francqui Foundation and an Incentive Grant for Scientific Research from the “Fonds de la Recherche Scientifique” (FNRS, MIS‐F.4540.21). Camille Lemaigre and Benjamin Ledoux are supported by PhD fellowships from FRIA/FNRS (Belgium). This work was also supported by the France BioImaging Infrastructure (French National Research Agency, ANR‐10 INBS‐04‐07, “Investments for the future”), the Labex DCBiol (ANR‐11‐LABX‐0043) and the Labex Cell(n)Scale (ANR‐11‐LABX‐0038) as part of the Idex PSL (ANR‐10‐IDEX‐0001‐02).

Funders	Funder number
Institut Curie
UCLouvain
Idex PSL
IREC
Fondation Francqui - Stichting
LIBST
Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture
Fédération Wallonie-Bruxelles
Fonds De La Recherche Scientifique - FNRS	CDR‐J.0119.19, MIS‐F.4540.21
Labex DCBiol	ANR‐11‐LABX‐0038
Labex Cell	ANR‐10‐IDEX‐0001‐02
Communauté française de Belgique–Actions de Recherches Concertées	17/22‐085
Agence Nationale de la Recherche	ANR-11-LABX-0043, ANR‐10 INBS‐04‐07

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Clathrin/metabolism
Neural Cell Adhesion Molecule L1
Protein Isoforms
Endocytosis/physiology
Galectins
PSTPIP1
galectin
endophilin-A3
BAR domain proteins
L1CAM
Clathrin-independent endocytosis

Access to Document

10.1111/tra.12883Licence: CC BY-NC-ND

Cite this

@article{42037d16d2224aee94237f381fbd67f5,

title = "N-BAR and F-BAR proteins-endophilin-A3 and PSTPIP1-control clathrin-independent endocytosis of L1CAM",

abstract = "Recent advances in the field demonstrate the high diversity and complexity of endocytic pathways. In the current study, we focus on the endocytosis of L1CAM. This glycoprotein plays a major role in the development of the nervous system, and is involved in cancer development and is associated with metastases and poor prognosis. Two L1CAM isoforms are subject to endocytosis: isoform 1, described as a clathrin-mediated cargo; isoform 2, whose endocytosis has never been studied. Deciphering the molecular machinery of isoform 2 internalisation should contribute to a better understanding of its pathophysiological role. First, we demonstrated in our cellular context that both isoforms of L1CAM are mainly a clathrin-independent cargo, which was not expected for isoform 1. Second, the mechanism of L1CAM endocytosis is specifically mediated by the N-BAR domain protein endophilin-A3. Third, we discovered PSTPIP1, an F-BAR domain protein, as a novel actor in this endocytic process. Finally, we identified galectins as endocytic partners and negative regulators of L1CAM endocytosis. In summary, the interplay of the BAR proteins endophilin-A3 and PSTPIP1, and galectins fine tune the clathrin-independent endocytosis of L1CAM.",

keywords = "Clathrin/metabolism, Neural Cell Adhesion Molecule L1, Protein Isoforms, Endocytosis/physiology, Galectins, PSTPIP1, galectin, endophilin-A3, BAR domain proteins, L1CAM, Clathrin-independent endocytosis",

author = "Camille Lemaigre and Apolline Ceuppens and Valades-Cruz, \{Cesar Augusto\} and Benjamin Ledoux and Bastien Vanbeneden and Mujtaba Hassan and Zetterberg, \{Fredrik R\} and Nilsson, \{Ulf J\} and Ludger Johannes and Christian Wunder and Henri-Fran{\c c}ois Renard and Pierre Morsomme",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Traffic published by John Wiley \& Sons Ltd.",

year = "2023",

month = apr,

doi = "10.1111/tra.12883",

language = "English",

volume = "24",

pages = "190--212",

journal = "Traffic",

issn = "1398-9219",

publisher = "Blackwell Munksgaard",

number = "4",

}

TY - JOUR

T1 - N-BAR and F-BAR proteins-endophilin-A3 and PSTPIP1-control clathrin-independent endocytosis of L1CAM

AU - Lemaigre, Camille

AU - Ceuppens, Apolline

AU - Valades-Cruz, Cesar Augusto

AU - Ledoux, Benjamin

AU - Vanbeneden, Bastien

AU - Hassan, Mujtaba

AU - Zetterberg, Fredrik R

AU - Nilsson, Ulf J

AU - Johannes, Ludger

AU - Wunder, Christian

AU - Renard, Henri-François

AU - Morsomme, Pierre

PY - 2023/4

Y1 - 2023/4

N2 - Recent advances in the field demonstrate the high diversity and complexity of endocytic pathways. In the current study, we focus on the endocytosis of L1CAM. This glycoprotein plays a major role in the development of the nervous system, and is involved in cancer development and is associated with metastases and poor prognosis. Two L1CAM isoforms are subject to endocytosis: isoform 1, described as a clathrin-mediated cargo; isoform 2, whose endocytosis has never been studied. Deciphering the molecular machinery of isoform 2 internalisation should contribute to a better understanding of its pathophysiological role. First, we demonstrated in our cellular context that both isoforms of L1CAM are mainly a clathrin-independent cargo, which was not expected for isoform 1. Second, the mechanism of L1CAM endocytosis is specifically mediated by the N-BAR domain protein endophilin-A3. Third, we discovered PSTPIP1, an F-BAR domain protein, as a novel actor in this endocytic process. Finally, we identified galectins as endocytic partners and negative regulators of L1CAM endocytosis. In summary, the interplay of the BAR proteins endophilin-A3 and PSTPIP1, and galectins fine tune the clathrin-independent endocytosis of L1CAM.

AB - Recent advances in the field demonstrate the high diversity and complexity of endocytic pathways. In the current study, we focus on the endocytosis of L1CAM. This glycoprotein plays a major role in the development of the nervous system, and is involved in cancer development and is associated with metastases and poor prognosis. Two L1CAM isoforms are subject to endocytosis: isoform 1, described as a clathrin-mediated cargo; isoform 2, whose endocytosis has never been studied. Deciphering the molecular machinery of isoform 2 internalisation should contribute to a better understanding of its pathophysiological role. First, we demonstrated in our cellular context that both isoforms of L1CAM are mainly a clathrin-independent cargo, which was not expected for isoform 1. Second, the mechanism of L1CAM endocytosis is specifically mediated by the N-BAR domain protein endophilin-A3. Third, we discovered PSTPIP1, an F-BAR domain protein, as a novel actor in this endocytic process. Finally, we identified galectins as endocytic partners and negative regulators of L1CAM endocytosis. In summary, the interplay of the BAR proteins endophilin-A3 and PSTPIP1, and galectins fine tune the clathrin-independent endocytosis of L1CAM.

KW - Clathrin/metabolism

KW - Neural Cell Adhesion Molecule L1

KW - Protein Isoforms

KW - Endocytosis/physiology

KW - Galectins

KW - PSTPIP1

KW - galectin

KW - endophilin-A3

KW - BAR domain proteins

KW - L1CAM

KW - Clathrin-independent endocytosis

UR - https://www.scopus.com/pages/publications/85149742218

U2 - 10.1111/tra.12883

DO - 10.1111/tra.12883

M3 - Article

C2 - 36843549

SN - 1398-9219

VL - 24

SP - 190

EP - 212

JO - Traffic

JF - Traffic

IS - 4

ER -

N-BAR and F-BAR proteins-endophilin-A3 and PSTPIP1-control clathrin-independent endocytosis of L1CAM

Abstract

Funding

UN SDGs

Keywords

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Morphology - Imaging

Cite this

N-BAR and F-BAR proteins-endophilin-A3 and PSTPIP1-control clathrin-independent endocytosis of L1CAM

Abstract

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Equipment

Morphology - Imaging

Cite this