PTEN suppresses axon outgrowth by downregulating the level of detyrosinated microtubules

Christina Kath, Paloma Goni-Oliver, Rainer Müller, Carsten Schultz, Volker Haucke, Britta Eickholt, Jan Schmoranzer

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Inhibition of the phospholipid phosphatase and tumor suppressor PTEN leads to excessive polarized cell growth during directed cell migration and neurite outgrowth. These processes require the precise regulation of both the actin and microtubule cytoskeleton. While PTEN is known to regulate actin dynamics through phospholipid modulation, whether and how PTEN regulates microtubule dynamics is unknown. Here, we show that depletion of PTEN leads to elevated levels of stable and post-translationally modified (detyrosinated) microtubules in fibroblasts and developing neurons. Further, PTEN depletion enhanced axon outgrowth, which was rescued by reducing the level of detyrosinated microtubules. These data demonstrate a novel role of PTEN in regulating the microtubule cytoskeleton. They further show a novel function of detyrosinated microtubules in axon outgrowth. Specifically, PTEN suppresses axon outgrowth by down-regulating the level of detyrosinated microtubules. Our results suggest that PTEN’s role in preventing excessive cell growth in cancerous and neurodevelopmental phenotypes is partially exerted by stabilization and detyrosination of the microtubule cytoskeleton.

Original languageEnglish (US)
Article numbere0193257
JournalPLoS One
Volume13
Issue number4
DOIs
StatePublished - Apr 1 2018
Externally publishedYes

Fingerprint

axons
Microtubules
microtubules
Down-Regulation
Cell growth
Actins
Phospholipids
cytoskeleton
Fibroblasts
Phosphoric Monoester Hydrolases
Neurons
Tumors
Stabilization
Cytoskeleton
Modulation
actin
cell growth
phospholipids
neurites
Axons

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kath, C., Goni-Oliver, P., Müller, R., Schultz, C., Haucke, V., Eickholt, B., & Schmoranzer, J. (2018). PTEN suppresses axon outgrowth by downregulating the level of detyrosinated microtubules. PLoS One, 13(4), [e0193257]. https://doi.org/10.1371/journal.pone.0193257

PTEN suppresses axon outgrowth by downregulating the level of detyrosinated microtubules. / Kath, Christina; Goni-Oliver, Paloma; Müller, Rainer; Schultz, Carsten; Haucke, Volker; Eickholt, Britta; Schmoranzer, Jan.

In: PLoS One, Vol. 13, No. 4, e0193257, 01.04.2018.

Research output: Contribution to journalArticle

Kath, C, Goni-Oliver, P, Müller, R, Schultz, C, Haucke, V, Eickholt, B & Schmoranzer, J 2018, 'PTEN suppresses axon outgrowth by downregulating the level of detyrosinated microtubules', PLoS One, vol. 13, no. 4, e0193257. https://doi.org/10.1371/journal.pone.0193257
Kath, Christina ; Goni-Oliver, Paloma ; Müller, Rainer ; Schultz, Carsten ; Haucke, Volker ; Eickholt, Britta ; Schmoranzer, Jan. / PTEN suppresses axon outgrowth by downregulating the level of detyrosinated microtubules. In: PLoS One. 2018 ; Vol. 13, No. 4.
@article{19312add0621403aa6d1c042b97eb65f,
title = "PTEN suppresses axon outgrowth by downregulating the level of detyrosinated microtubules",
abstract = "Inhibition of the phospholipid phosphatase and tumor suppressor PTEN leads to excessive polarized cell growth during directed cell migration and neurite outgrowth. These processes require the precise regulation of both the actin and microtubule cytoskeleton. While PTEN is known to regulate actin dynamics through phospholipid modulation, whether and how PTEN regulates microtubule dynamics is unknown. Here, we show that depletion of PTEN leads to elevated levels of stable and post-translationally modified (detyrosinated) microtubules in fibroblasts and developing neurons. Further, PTEN depletion enhanced axon outgrowth, which was rescued by reducing the level of detyrosinated microtubules. These data demonstrate a novel role of PTEN in regulating the microtubule cytoskeleton. They further show a novel function of detyrosinated microtubules in axon outgrowth. Specifically, PTEN suppresses axon outgrowth by down-regulating the level of detyrosinated microtubules. Our results suggest that PTEN’s role in preventing excessive cell growth in cancerous and neurodevelopmental phenotypes is partially exerted by stabilization and detyrosination of the microtubule cytoskeleton.",
author = "Christina Kath and Paloma Goni-Oliver and Rainer M{\"u}ller and Carsten Schultz and Volker Haucke and Britta Eickholt and Jan Schmoranzer",
year = "2018",
month = "4",
day = "1",
doi = "10.1371/journal.pone.0193257",
language = "English (US)",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - PTEN suppresses axon outgrowth by downregulating the level of detyrosinated microtubules

AU - Kath, Christina

AU - Goni-Oliver, Paloma

AU - Müller, Rainer

AU - Schultz, Carsten

AU - Haucke, Volker

AU - Eickholt, Britta

AU - Schmoranzer, Jan

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Inhibition of the phospholipid phosphatase and tumor suppressor PTEN leads to excessive polarized cell growth during directed cell migration and neurite outgrowth. These processes require the precise regulation of both the actin and microtubule cytoskeleton. While PTEN is known to regulate actin dynamics through phospholipid modulation, whether and how PTEN regulates microtubule dynamics is unknown. Here, we show that depletion of PTEN leads to elevated levels of stable and post-translationally modified (detyrosinated) microtubules in fibroblasts and developing neurons. Further, PTEN depletion enhanced axon outgrowth, which was rescued by reducing the level of detyrosinated microtubules. These data demonstrate a novel role of PTEN in regulating the microtubule cytoskeleton. They further show a novel function of detyrosinated microtubules in axon outgrowth. Specifically, PTEN suppresses axon outgrowth by down-regulating the level of detyrosinated microtubules. Our results suggest that PTEN’s role in preventing excessive cell growth in cancerous and neurodevelopmental phenotypes is partially exerted by stabilization and detyrosination of the microtubule cytoskeleton.

AB - Inhibition of the phospholipid phosphatase and tumor suppressor PTEN leads to excessive polarized cell growth during directed cell migration and neurite outgrowth. These processes require the precise regulation of both the actin and microtubule cytoskeleton. While PTEN is known to regulate actin dynamics through phospholipid modulation, whether and how PTEN regulates microtubule dynamics is unknown. Here, we show that depletion of PTEN leads to elevated levels of stable and post-translationally modified (detyrosinated) microtubules in fibroblasts and developing neurons. Further, PTEN depletion enhanced axon outgrowth, which was rescued by reducing the level of detyrosinated microtubules. These data demonstrate a novel role of PTEN in regulating the microtubule cytoskeleton. They further show a novel function of detyrosinated microtubules in axon outgrowth. Specifically, PTEN suppresses axon outgrowth by down-regulating the level of detyrosinated microtubules. Our results suggest that PTEN’s role in preventing excessive cell growth in cancerous and neurodevelopmental phenotypes is partially exerted by stabilization and detyrosination of the microtubule cytoskeleton.

UR - http://www.scopus.com/inward/record.url?scp=85045010747&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045010747&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0193257

DO - 10.1371/journal.pone.0193257

M3 - Article

C2 - 29617365

AN - SCOPUS:85045010747

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e0193257

ER -