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A novel sterol-binding protein reveals heterogeneous cholesterol distribution in neurite outgrowth and in late endosomes/lysosomes

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Abstract

We identified a mushroom-derived protein, maistero-2 that specifically binds 3-hydroxy sterol including cholesterol (Chol). Maistero-2 bound lipid mixture in Chol-dependent manner with a binding threshold of around 30%. Changing lipid composition did not significantly affect the threshold concentration. EGFP-maistero-2 labeled cell surface and intracellular organelle Chol with higher sensitivity than that of well-established Chol probe, D4 fragment of perfringolysin O. EGFP-maistero-2 revealed increase of cell surface Chol during neurite outgrowth and heterogeneous Chol distribution between CD63-positive and LAMP1-positive late endosomes/lysosomes. The absence of strictly conserved Thr-Leu pair present in Chol-dependent cytolysins suggests a distinct Chol-binding mechanism for maistero-2.

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Data and materials availability

The data sets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ALO:

Anthrolysin O

BSA:

Bovine serum albumin

Chol:

Cholesterol

CD:

Circular dichroism

CDC:

Cholesterol-dependent cytolysin

CHO:

Chinese hamster ovary

CRAC:

Cholesterol recognition/interaction amino acid consensus

DIC:

Differential interference contrast

DMEM:

Dulbecco’s modified Eagle’s medium

DOPC:

1,2-Dioleoyl-sn-glycero-3-phosphocholine

EGFP:

Enhanced green fluorescent protein

ELISA:

Enzyme-linked immunosorbent assay

ER:

Endoplasmic reticulum

FCS:

Fetal calf serum

LDL:

Low density lipoprotein

mAb:

Mouse monoclonal antibody

MβCD:

Methyl-beta-cyclodextrin

MLV:

Multilamellar vesicle

NBD-DOPE:

1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2–1,3-benzoxadiazol-4-yl)

NBD-DPPE:

1,2-Dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2–1,3-benzoxadiazol-4-yl)

NPC:

Niemann–Pick disease type C

PBS:

Phosphate buffered saline

PC:

Phosphatidylcholine

PFA:

Paraformaldehyde

PFO:

Perfringolysin O

POPC:

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine

POPE:

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine

QCM:

Quartz crystal microbalance

SM:

Sphingomyelin

SUV:

Small unilamellar vesicle

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Acknowledgements

We are grateful to Ms. Nozomi Yoshida for excellent technical assistance. We thank Dr. Takuma Kishimoto for providing mCherry-D4. CD spectral measurements were supported by Molecular Structure Characterization Unit, RIKEN Center for Sustainable Resource Science (CSRS). We are grateful to Dr. Hubert Schaller, Institut de Biologie Moléculaire des Plantes, UPR 2357, CNRS, Université de Strasbourg, for providing us sterols.

Funding

Agence Nationale pour la Recherche (ANR-19-CE16-0012–02 to T.K.). Agence Nationale de Recherche sur le Sida et les Hépatites virale (18365 to T.K.). Ligue Contre le Cancer (to T.K.). Vaincre les Maladies Lysosomales (19/LBPH/S44 to T.K.). Seed Money, Assemblée du groupement européen de coopération territoriale (GECT) Eucor (to T.K.). Japan Society for the Promotion of Science (JSPS) (18K06648 to A. Y-H). RIKEN Integrated Lipidology Program (to A. Y-H, P.G. and T.K.). RIKEN Glycolipidologue Initiative Program (to T.K. Y.S. and P.G.). Institut national de la santé et de la recherche médicale (Inserm) (to T.K.). Centre national de la recherche scientifique (CNRS) (to T.K.). Université de Strasbourg (to T.K.)

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Authors and Affiliations

  1. Lipid Biology Laboratory, RIKEN, 2-1, Hirosawa, Wako-shi, Saitama, 351-0198, Japan

    Akiko Yamaji-Hasegawa, Motohide Murate, Takehiko Inaba, Peter Greimel & Toshihide Kobayashi

  2. Cellular Informatics Laboratory, RIKEN CPR, 2-1, Hirosawa, Wako-shi, Saitama, 351-0198, Japan

    Motohide Murate, Takehiko Inaba, Yasushi Sako & Toshihide Kobayashi

  3. UMR 7021, CNRS, Université de Strasbourg, 67401, Illkirch, France

    Motohide Murate & Toshihide Kobayashi

  4. Biomolecular Characterization Unit, RIKEN CSRS, 2-1, Hirosawa, Wako-shi, Saitama, 351-0198, Japan

    Naoshi Dohmae

  5. Yukiguni Maitake Co, Ltd. Yokawa 89, Minamiuonuma, Niigata, 949-6695, Japan

    Masayuki Sato

  6. Laboratory of Biological Science and Technology, Tokyo Kasei University, 1-18-1 Kaga, Itabashi, Tokyo, 173-8062, Japan

    Fumihiro Fujimori

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  1. Akiko Yamaji-Hasegawa
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  9. Toshihide Kobayashi
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Contributions

Conception and design of the research: AY-H, TK. Investigation: AY-H, MM, TI, ND, MS, FF, PG. Methodology: TI, ND, FF. Supervision: TK. Writing-original draft: AY-H, PG, TK. Writing-review and editing: AY-H, MM, TI, ND, MS, FF, YS, PG, TK.

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Correspondence to Akiko Yamaji-Hasegawa or Toshihide Kobayashi.

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Yamaji-Hasegawa, A., Murate, M., Inaba, T. et al. A novel sterol-binding protein reveals heterogeneous cholesterol distribution in neurite outgrowth and in late endosomes/lysosomes. Cell. Mol. Life Sci. 79, 324 (2022). https://doi.org/10.1007/s00018-022-04339-6

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