Regulation of lipid-droplet transport by the perilipin homolog LSD2

Michael A. Welte, Silvia Cermelli, John Griner, Arturo Viera, Yi D Guo, Dae Hwan Kim, Joseph G. Gindhart, Steven P. Gross

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Background: Motor-driven transport along microtubules is a primary mechanism for moving and positioning organelles. How such transport is regulated remains poorly understood. For lipid droplets in Drosophila embryos, three distinct phases of transport can be distinguished. To identify factors regulating this transport, we biochemically purified droplets from individual phases and used 2D gel analysis to search for proteins whose amount on droplets changes as motion changes. Results: By mass spectrometry, we identified one such protein as LSD2. Similar to its mammalian counterpart Perilipin, LSD2 is responsible for regulating lipid homeostasis. Using specific antibodies, we confirmed that LSD2 is present on embryonic lipid droplets. We find that lack of LSD2 causes a specific transport defect: Droplet distribution fails to undergo the dramatic changes characteristic of the wild-type. This defect is not due to a complete failure of the core transport machinery - individual droplets still move bidirectionally along microtubules with approximately normal velocities and kinetics. Rather, detailed biophysical analysis suggests that developmental control of droplet motion is lost. We show that LSD2 is multiply phosphorylated in a developmentally controlled manner. LSD2 phosphorylation depends on the transacting signal Halo, and LSD2 can physically interact with the lipid-droplet-associated coordinator Klar, identifying LSD2 as a central player in the mechanisms that control droplet motion. Conclusions: LSD2 appears to represent a new class of regulators, a protein that transduces regulatory signals to a separable core motor machinery. In addition, the demonstration that LSD2 regulates both transport and lipid metabolism suggests a link between lipid-droplet motion and lipid homeostasis.

Original languageEnglish (US)
Pages (from-to)1266-1275
Number of pages10
JournalCurrent Biology
Volume15
Issue number14
DOIs
StatePublished - Jul 26 2005
Externally publishedYes

Fingerprint

droplets
Lipids
lipids
Microtubules
Homeostasis
Proteins
Lipid Metabolism
Organelles
Drosophila
Mass Spectrometry
Embryonic Structures
Gels
Phosphorylation
microtubules
Machinery
homeostasis
Perilipin-1
Lipid Droplets
Antibodies
Defects

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Welte, M. A., Cermelli, S., Griner, J., Viera, A., Guo, Y. D., Kim, D. H., ... Gross, S. P. (2005). Regulation of lipid-droplet transport by the perilipin homolog LSD2. Current Biology, 15(14), 1266-1275. https://doi.org/10.1016/j.cub.2005.06.062

Regulation of lipid-droplet transport by the perilipin homolog LSD2. / Welte, Michael A.; Cermelli, Silvia; Griner, John; Viera, Arturo; Guo, Yi D; Kim, Dae Hwan; Gindhart, Joseph G.; Gross, Steven P.

In: Current Biology, Vol. 15, No. 14, 26.07.2005, p. 1266-1275.

Research output: Contribution to journalArticle

Welte, MA, Cermelli, S, Griner, J, Viera, A, Guo, YD, Kim, DH, Gindhart, JG & Gross, SP 2005, 'Regulation of lipid-droplet transport by the perilipin homolog LSD2', Current Biology, vol. 15, no. 14, pp. 1266-1275. https://doi.org/10.1016/j.cub.2005.06.062
Welte MA, Cermelli S, Griner J, Viera A, Guo YD, Kim DH et al. Regulation of lipid-droplet transport by the perilipin homolog LSD2. Current Biology. 2005 Jul 26;15(14):1266-1275. https://doi.org/10.1016/j.cub.2005.06.062
Welte, Michael A. ; Cermelli, Silvia ; Griner, John ; Viera, Arturo ; Guo, Yi D ; Kim, Dae Hwan ; Gindhart, Joseph G. ; Gross, Steven P. / Regulation of lipid-droplet transport by the perilipin homolog LSD2. In: Current Biology. 2005 ; Vol. 15, No. 14. pp. 1266-1275.
@article{1ef1e4ab95964455ba7a63fec178cb20,
title = "Regulation of lipid-droplet transport by the perilipin homolog LSD2",
abstract = "Background: Motor-driven transport along microtubules is a primary mechanism for moving and positioning organelles. How such transport is regulated remains poorly understood. For lipid droplets in Drosophila embryos, three distinct phases of transport can be distinguished. To identify factors regulating this transport, we biochemically purified droplets from individual phases and used 2D gel analysis to search for proteins whose amount on droplets changes as motion changes. Results: By mass spectrometry, we identified one such protein as LSD2. Similar to its mammalian counterpart Perilipin, LSD2 is responsible for regulating lipid homeostasis. Using specific antibodies, we confirmed that LSD2 is present on embryonic lipid droplets. We find that lack of LSD2 causes a specific transport defect: Droplet distribution fails to undergo the dramatic changes characteristic of the wild-type. This defect is not due to a complete failure of the core transport machinery - individual droplets still move bidirectionally along microtubules with approximately normal velocities and kinetics. Rather, detailed biophysical analysis suggests that developmental control of droplet motion is lost. We show that LSD2 is multiply phosphorylated in a developmentally controlled manner. LSD2 phosphorylation depends on the transacting signal Halo, and LSD2 can physically interact with the lipid-droplet-associated coordinator Klar, identifying LSD2 as a central player in the mechanisms that control droplet motion. Conclusions: LSD2 appears to represent a new class of regulators, a protein that transduces regulatory signals to a separable core motor machinery. In addition, the demonstration that LSD2 regulates both transport and lipid metabolism suggests a link between lipid-droplet motion and lipid homeostasis.",
author = "Welte, {Michael A.} and Silvia Cermelli and John Griner and Arturo Viera and Guo, {Yi D} and Kim, {Dae Hwan} and Gindhart, {Joseph G.} and Gross, {Steven P.}",
year = "2005",
month = "7",
day = "26",
doi = "10.1016/j.cub.2005.06.062",
language = "English (US)",
volume = "15",
pages = "1266--1275",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "14",

}

TY - JOUR

T1 - Regulation of lipid-droplet transport by the perilipin homolog LSD2

AU - Welte, Michael A.

AU - Cermelli, Silvia

AU - Griner, John

AU - Viera, Arturo

AU - Guo, Yi D

AU - Kim, Dae Hwan

AU - Gindhart, Joseph G.

AU - Gross, Steven P.

PY - 2005/7/26

Y1 - 2005/7/26

N2 - Background: Motor-driven transport along microtubules is a primary mechanism for moving and positioning organelles. How such transport is regulated remains poorly understood. For lipid droplets in Drosophila embryos, three distinct phases of transport can be distinguished. To identify factors regulating this transport, we biochemically purified droplets from individual phases and used 2D gel analysis to search for proteins whose amount on droplets changes as motion changes. Results: By mass spectrometry, we identified one such protein as LSD2. Similar to its mammalian counterpart Perilipin, LSD2 is responsible for regulating lipid homeostasis. Using specific antibodies, we confirmed that LSD2 is present on embryonic lipid droplets. We find that lack of LSD2 causes a specific transport defect: Droplet distribution fails to undergo the dramatic changes characteristic of the wild-type. This defect is not due to a complete failure of the core transport machinery - individual droplets still move bidirectionally along microtubules with approximately normal velocities and kinetics. Rather, detailed biophysical analysis suggests that developmental control of droplet motion is lost. We show that LSD2 is multiply phosphorylated in a developmentally controlled manner. LSD2 phosphorylation depends on the transacting signal Halo, and LSD2 can physically interact with the lipid-droplet-associated coordinator Klar, identifying LSD2 as a central player in the mechanisms that control droplet motion. Conclusions: LSD2 appears to represent a new class of regulators, a protein that transduces regulatory signals to a separable core motor machinery. In addition, the demonstration that LSD2 regulates both transport and lipid metabolism suggests a link between lipid-droplet motion and lipid homeostasis.

AB - Background: Motor-driven transport along microtubules is a primary mechanism for moving and positioning organelles. How such transport is regulated remains poorly understood. For lipid droplets in Drosophila embryos, three distinct phases of transport can be distinguished. To identify factors regulating this transport, we biochemically purified droplets from individual phases and used 2D gel analysis to search for proteins whose amount on droplets changes as motion changes. Results: By mass spectrometry, we identified one such protein as LSD2. Similar to its mammalian counterpart Perilipin, LSD2 is responsible for regulating lipid homeostasis. Using specific antibodies, we confirmed that LSD2 is present on embryonic lipid droplets. We find that lack of LSD2 causes a specific transport defect: Droplet distribution fails to undergo the dramatic changes characteristic of the wild-type. This defect is not due to a complete failure of the core transport machinery - individual droplets still move bidirectionally along microtubules with approximately normal velocities and kinetics. Rather, detailed biophysical analysis suggests that developmental control of droplet motion is lost. We show that LSD2 is multiply phosphorylated in a developmentally controlled manner. LSD2 phosphorylation depends on the transacting signal Halo, and LSD2 can physically interact with the lipid-droplet-associated coordinator Klar, identifying LSD2 as a central player in the mechanisms that control droplet motion. Conclusions: LSD2 appears to represent a new class of regulators, a protein that transduces regulatory signals to a separable core motor machinery. In addition, the demonstration that LSD2 regulates both transport and lipid metabolism suggests a link between lipid-droplet motion and lipid homeostasis.

UR - http://www.scopus.com/inward/record.url?scp=22744434906&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22744434906&partnerID=8YFLogxK

U2 - 10.1016/j.cub.2005.06.062

DO - 10.1016/j.cub.2005.06.062

M3 - Article

C2 - 16051169

AN - SCOPUS:22744434906

VL - 15

SP - 1266

EP - 1275

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 14

ER -