Proximity Ligation Mapping of Microcephaly Associated SMPD4 Shows Association with Components of the Nuclear Pore Membrane

Alexandra C.A. Piët; Marco Post; Dick Dekkers; Jeroen A.A. Demmers; Maarten Fornerod

doi:10.3390/cells11040674

Proximity Ligation Mapping of Microcephaly Associated SMPD4 Shows Association with Components of the Nuclear Pore Membrane

Alexandra C.A. Piët, Marco Post, Dick Dekkers, Jeroen A.A. Demmers, Maarten Fornerod^*

^*Corresponding author for this work

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

8 Citations (Scopus)

36 Downloads (Pure)

Abstract

SMPD4 is a neutral sphingomyelinase implicated in a specific type of congenital microcephaly. Although not intensively studied, SMPD4 deficiency has also been found to cause cell division defects. This suggests a role for SMPD4 in cell-cycle and differentiation. In order to explore this role, we used proximity ligation to identify the partners of SMPD4 in vivo in HEK293T cells. We found that these partners localize near the endoplasmic reticulum (ER) and the nuclear membrane. Using mass spectrometry, we could identify these partners and discovered that SMPD4 is closely associated with several nucleoporins, including NUP35, a nucleoporin directly involved in pore membrane curvature and pore insertion. This suggests that SMPD4 may play a role in this process.

Original language	English
Article number	674
Journal	Cells
Volume	11
Issue number	4
DOIs	https://doi.org/10.3390/cells11040674
Publication status	Published - 15 Feb 2022

Bibliographical note

Funding Information:
Funding: This research was funded by the Netherlands Organization for Health Research and Development (ZonMW), grant number 91217045.

Funding Information:
This research was funded by the Netherlands Organization for Health Research and Development (ZonMW), grant number 91217045. We acknowledge Martijn de Gruiter and the ErasmusMC Optical Imaging Center for help with confocal image acquisition.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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Proximity Ligation Mapping of Microcephaly Associated SMPD4 Shows Association with Components of the Nuclear Pore MembraneFinal published version, 3.65 MBLicence: CC BY

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title = "Proximity Ligation Mapping of Microcephaly Associated SMPD4 Shows Association with Components of the Nuclear Pore Membrane",

abstract = "SMPD4 is a neutral sphingomyelinase implicated in a specific type of congenital microcephaly. Although not intensively studied, SMPD4 deficiency has also been found to cause cell division defects. This suggests a role for SMPD4 in cell-cycle and differentiation. In order to explore this role, we used proximity ligation to identify the partners of SMPD4 in vivo in HEK293T cells. We found that these partners localize near the endoplasmic reticulum (ER) and the nuclear membrane. Using mass spectrometry, we could identify these partners and discovered that SMPD4 is closely associated with several nucleoporins, including NUP35, a nucleoporin directly involved in pore membrane curvature and pore insertion. This suggests that SMPD4 may play a role in this process.",

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note = "Funding Information: Funding: This research was funded by the Netherlands Organization for Health Research and Development (ZonMW), grant number 91217045. Funding Information: This research was funded by the Netherlands Organization for Health Research and Development (ZonMW), grant number 91217045. We acknowledge Martijn de Gruiter and the ErasmusMC Optical Imaging Center for help with confocal image acquisition. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Demmers, Jeroen A.A.

AU - Fornerod, Maarten

N1 - Funding Information: Funding: This research was funded by the Netherlands Organization for Health Research and Development (ZonMW), grant number 91217045. Funding Information: This research was funded by the Netherlands Organization for Health Research and Development (ZonMW), grant number 91217045. We acknowledge Martijn de Gruiter and the ErasmusMC Optical Imaging Center for help with confocal image acquisition. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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N2 - SMPD4 is a neutral sphingomyelinase implicated in a specific type of congenital microcephaly. Although not intensively studied, SMPD4 deficiency has also been found to cause cell division defects. This suggests a role for SMPD4 in cell-cycle and differentiation. In order to explore this role, we used proximity ligation to identify the partners of SMPD4 in vivo in HEK293T cells. We found that these partners localize near the endoplasmic reticulum (ER) and the nuclear membrane. Using mass spectrometry, we could identify these partners and discovered that SMPD4 is closely associated with several nucleoporins, including NUP35, a nucleoporin directly involved in pore membrane curvature and pore insertion. This suggests that SMPD4 may play a role in this process.

AB - SMPD4 is a neutral sphingomyelinase implicated in a specific type of congenital microcephaly. Although not intensively studied, SMPD4 deficiency has also been found to cause cell division defects. This suggests a role for SMPD4 in cell-cycle and differentiation. In order to explore this role, we used proximity ligation to identify the partners of SMPD4 in vivo in HEK293T cells. We found that these partners localize near the endoplasmic reticulum (ER) and the nuclear membrane. Using mass spectrometry, we could identify these partners and discovered that SMPD4 is closely associated with several nucleoporins, including NUP35, a nucleoporin directly involved in pore membrane curvature and pore insertion. This suggests that SMPD4 may play a role in this process.

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Proximity Ligation Mapping of Microcephaly Associated SMPD4 Shows Association with Components of the Nuclear Pore Membrane

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