Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane Contact Site Proteins Interacting with FFAT-Related FFNT Motifs

Birol Cabukusta; Ilana Berlin; Daphne M van Elsland; Iris Forkink; Menno Spits; Anja W M de Jong; Jimmy J L L Akkermans; Ruud H M Wijdeven; George M C Janssen; Peter A van Veelen; Jacques Neefjes

doi:10.1016/j.celrep.2020.108475

Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane Contact Site Proteins Interacting with FFAT-Related FFNT Motifs

Birol Cabukusta
, Ilana Berlin
, Daphne M van Elsland
, Iris Forkink
, Menno Spits
, Anja W M de Jong
, Jimmy J L L Akkermans
, Ruud H M Wijdeven
, George M C Janssen
, Peter A van Veelen
, Jacques Neefjes

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

Abstract

Membrane contact sites (MCS) are intracellular regions where two organelles come closer to exchange information and material. The majority of the endoplasmic reticulum (ER) MCS are attributed to the ER-localized tether proteins VAPA, VAPB, and MOSPD2. These recruit other proteins to the ER by interacting with their FFAT motifs. Here, we describe MOSPD1 and MOSPD3 as ER-localized tethers interacting with FFAT motif-containing proteins. Using BioID, we identify proteins interacting with VAP and MOSPD proteins and find that MOSPD1 and MOSPD3 prefer unconventional FFAT-related FFNT (two phenylalanines [FF] in a neutral tract) motifs. Moreover, VAPA/VAPB/MOSPD2 and MOSPD1/MOSPD3 assemble into two separate ER-resident complexes to interact with FFAT and FFNT motifs, respectively. Because of their ability to interact with FFNT motifs, MOSPD1 and MOSPD3 could form MCS between the ER and other organelles. Collectively, these findings expand the VAP family of proteins and highlight two separate complexes in control of interactions between intracellular compartments.

Original language	English
Article number	108475
Journal	Cell Reports
Volume	33
Issue number	10
DOIs	https://doi.org/10.1016/j.celrep.2020.108475
Publication status	Published - 8 Dec 2020
Externally published	Yes

Keywords

Amino Acid Motifs/genetics
Cell Line
Cell Line, Tumor
Cell Membrane/metabolism
Endoplasmic Reticulum/genetics
Humans
Intracellular Signaling Peptides and Proteins/metabolism
Membrane Proteins/metabolism
Mitochondrial Membranes/metabolism
Protein Binding/genetics
Protein Interaction Domains and Motifs/genetics
Protein Interaction Mapping/methods
Vesicular Transport Proteins/metabolism

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10.1016/j.celrep.2020.108475Licence: CC BY-NC-ND

1 Erratum / corrigendum

Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane Contact Site Proteins Interacting with FFAT-Related FFNT Motifs [Correction]
Cabukusta, B., Berlin, I., van Elsland, D. M., Forkink, I., Spits, M., de Jong, A. W. M., Akkermans, J. J. L. L., Wijdeven, R. H. M., Janssen, G. M. C., van Veelen, P. A. & Neefjes, J., 25 Jul 2023, In: Cell Reports. 42, 7, 112849.
Research output: Contribution to journal › Erratum / corrigendum › Academic

Open Access

Cite this

Cabukusta, B., Berlin, I., van Elsland, D. M., Forkink, I., Spits, M., de Jong, A. W. M., Akkermans, J. J. L. L., Wijdeven, R. H. M., Janssen, G. M. C., van Veelen, P. A., & Neefjes, J. (2020). Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane Contact Site Proteins Interacting with FFAT-Related FFNT Motifs. Cell Reports, 33(10), Article 108475. https://doi.org/10.1016/j.celrep.2020.108475

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title = "Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane Contact Site Proteins Interacting with FFAT-Related FFNT Motifs",

abstract = "Membrane contact sites (MCS) are intracellular regions where two organelles come closer to exchange information and material. The majority of the endoplasmic reticulum (ER) MCS are attributed to the ER-localized tether proteins VAPA, VAPB, and MOSPD2. These recruit other proteins to the ER by interacting with their FFAT motifs. Here, we describe MOSPD1 and MOSPD3 as ER-localized tethers interacting with FFAT motif-containing proteins. Using BioID, we identify proteins interacting with VAP and MOSPD proteins and find that MOSPD1 and MOSPD3 prefer unconventional FFAT-related FFNT (two phenylalanines [FF] in a neutral tract) motifs. Moreover, VAPA/VAPB/MOSPD2 and MOSPD1/MOSPD3 assemble into two separate ER-resident complexes to interact with FFAT and FFNT motifs, respectively. Because of their ability to interact with FFNT motifs, MOSPD1 and MOSPD3 could form MCS between the ER and other organelles. Collectively, these findings expand the VAP family of proteins and highlight two separate complexes in control of interactions between intracellular compartments.",

keywords = "Amino Acid Motifs/genetics, Cell Line, Cell Line, Tumor, Cell Membrane/metabolism, Endoplasmic Reticulum/genetics, Humans, Intracellular Signaling Peptides and Proteins/metabolism, Membrane Proteins/metabolism, Mitochondrial Membranes/metabolism, Protein Binding/genetics, Protein Interaction Domains and Motifs/genetics, Protein Interaction Mapping/methods, Vesicular Transport Proteins/metabolism",

author = "Birol Cabukusta and Ilana Berlin and \{van Elsland\}, \{Daphne M\} and Iris Forkink and Menno Spits and \{de Jong\}, \{Anja W M\} and Akkermans, \{Jimmy J L L\} and Wijdeven, \{Ruud H M\} and Janssen, \{George M C\} and \{van Veelen\}, \{Peter A\} and Jacques Neefjes",

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T1 - Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane Contact Site Proteins Interacting with FFAT-Related FFNT Motifs

AU - Cabukusta, Birol

AU - Berlin, Ilana

AU - van Elsland, Daphne M

AU - Forkink, Iris

AU - Spits, Menno

AU - de Jong, Anja W M

AU - Akkermans, Jimmy J L L

AU - Wijdeven, Ruud H M

AU - Janssen, George M C

AU - van Veelen, Peter A

AU - Neefjes, Jacques

PY - 2020/12/8

Y1 - 2020/12/8

N2 - Membrane contact sites (MCS) are intracellular regions where two organelles come closer to exchange information and material. The majority of the endoplasmic reticulum (ER) MCS are attributed to the ER-localized tether proteins VAPA, VAPB, and MOSPD2. These recruit other proteins to the ER by interacting with their FFAT motifs. Here, we describe MOSPD1 and MOSPD3 as ER-localized tethers interacting with FFAT motif-containing proteins. Using BioID, we identify proteins interacting with VAP and MOSPD proteins and find that MOSPD1 and MOSPD3 prefer unconventional FFAT-related FFNT (two phenylalanines [FF] in a neutral tract) motifs. Moreover, VAPA/VAPB/MOSPD2 and MOSPD1/MOSPD3 assemble into two separate ER-resident complexes to interact with FFAT and FFNT motifs, respectively. Because of their ability to interact with FFNT motifs, MOSPD1 and MOSPD3 could form MCS between the ER and other organelles. Collectively, these findings expand the VAP family of proteins and highlight two separate complexes in control of interactions between intracellular compartments.

AB - Membrane contact sites (MCS) are intracellular regions where two organelles come closer to exchange information and material. The majority of the endoplasmic reticulum (ER) MCS are attributed to the ER-localized tether proteins VAPA, VAPB, and MOSPD2. These recruit other proteins to the ER by interacting with their FFAT motifs. Here, we describe MOSPD1 and MOSPD3 as ER-localized tethers interacting with FFAT motif-containing proteins. Using BioID, we identify proteins interacting with VAP and MOSPD proteins and find that MOSPD1 and MOSPD3 prefer unconventional FFAT-related FFNT (two phenylalanines [FF] in a neutral tract) motifs. Moreover, VAPA/VAPB/MOSPD2 and MOSPD1/MOSPD3 assemble into two separate ER-resident complexes to interact with FFAT and FFNT motifs, respectively. Because of their ability to interact with FFNT motifs, MOSPD1 and MOSPD3 could form MCS between the ER and other organelles. Collectively, these findings expand the VAP family of proteins and highlight two separate complexes in control of interactions between intracellular compartments.

KW - Amino Acid Motifs/genetics

KW - Cell Line

KW - Cell Line, Tumor

KW - Cell Membrane/metabolism

KW - Endoplasmic Reticulum/genetics

KW - Humans

KW - Intracellular Signaling Peptides and Proteins/metabolism

KW - Membrane Proteins/metabolism

KW - Mitochondrial Membranes/metabolism

KW - Protein Binding/genetics

KW - Protein Interaction Domains and Motifs/genetics

KW - Protein Interaction Mapping/methods

KW - Vesicular Transport Proteins/metabolism

U2 - 10.1016/j.celrep.2020.108475

DO - 10.1016/j.celrep.2020.108475

M3 - Article

C2 - 33296653

SN - 2639-1856

VL - 33

JO - Cell Reports

JF - Cell Reports

IS - 10

M1 - 108475

ER -

Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane Contact Site Proteins Interacting with FFAT-Related FFNT Motifs

Abstract

Keywords

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Research output

Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane Contact Site Proteins Interacting with FFAT-Related FFNT Motifs [Correction]

Cite this