Extracellular signal-regulated kinase regulates clathrin-independent endosomal trafficking

Sarah E. Robertson, Subba Rao Gangi Setty, Anand Sitaram, Michael S. Marks, Robert E Lewis, Margaret M. Chou

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Extracellular signal-regulated kinase (Erk) is widely recognized for its central role in cell proliferation and motility. Although previous work has shown that Erk is localized at endosomal compartments, no role for Erk in regulating endosomal trafficking has been demonstrated. Here, we report that Erk signaling regulates trafficking through the clathrin-independent, ADP-ribosylation factor 6 (Arf6) GTPase-regulated endosomal pathway. Inactivation of Erk induced by a variety of methods leads to a dramatic expansion of the Arf6 endosomal recycling compartment, and intracellular accumulation of cargo, such as class I major histocompatibility complex, within the expanded endosome. Treatment of cells with the mitogen-activated protein kinase kinase (MEK) inhibitor U0126 reduces surface expression of MHCI without affecting its rate of endocytosis, suggesting that inactivation of Erk perturbs recycling. Furthermore, under conditions where Erk activity is inhibited, a large cohort of Erk, MEK, and the Erk scaffold kinase suppressor of Ras 1 accumulates at the Arf6 recycling compartment. The requirement for Erk was highly specific for this endocytic pathway, because its inhibition had no effect on trafficking of cargo of the classical clathrin-dependent pathway. These studies reveal a previously unappreciated link of Erk signaling to organelle dynamics and endosomal trafficking.

Original languageEnglish (US)
Pages (from-to)645-657
Number of pages13
JournalMolecular biology of the cell
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2006

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Clathrin
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinase Kinases
Recycling
Endosomes
GTP Phosphohydrolases
Endocytosis
Major Histocompatibility Complex
Organelles
Cell Movement
Cell Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Extracellular signal-regulated kinase regulates clathrin-independent endosomal trafficking. / Robertson, Sarah E.; Setty, Subba Rao Gangi; Sitaram, Anand; Marks, Michael S.; Lewis, Robert E; Chou, Margaret M.

In: Molecular biology of the cell, Vol. 17, No. 2, 01.02.2006, p. 645-657.

Research output: Contribution to journalArticle

Robertson, Sarah E. ; Setty, Subba Rao Gangi ; Sitaram, Anand ; Marks, Michael S. ; Lewis, Robert E ; Chou, Margaret M. / Extracellular signal-regulated kinase regulates clathrin-independent endosomal trafficking. In: Molecular biology of the cell. 2006 ; Vol. 17, No. 2. pp. 645-657.
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