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Endosomes are ready and APPL to signal

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Activation of Rab5 by binding of extracellular factors such as EGF to their receptors stimulates endocytosis... Zerial's group shows that some EGF-containing endosomes trigger nuclear responses via two newly identified Rab effectors, APPL1 and APPL2... Thus, EGF can elicit signal transduction cascades from both endosomes and the plasma membrane... The APPL proteins were found in a unique subset of Rab5- and EGF-containing endosomes... GTP hydrolysis by Rab5 then released APPLs from the membranes so that they could enter the nucleus... There, APPLs interacted with a histone deacetylase and chromatin-remodeling proteins that are needed for cell cycle progression—and thus EGF's proliferative effects... Loss of APPL or its interaction with Rab5 blocked DNA synthesis and cell proliferation... Besides EGF, oxidative stress also relocated APPLs to the nucleus, and the authors believe that other growth factors will have the same effect... Miaczynska is now interested in determining whether the APPL-containing membranes are simply transport vesicles, subcompartments of early endosomes, or bona fide organelles. “If an organelle linked to endocytosis exists that is dedicated to signaling, it would increase the possibilities of regulation in the cell,” says Zerial. “It would explain why different cells respond so differently to growth factors, because the amount of this pathway differs... In essence, the ability of a cell to respond to growth factors depends not only on the set of receptors and signaling molecules but also on their trafficking pathways. ” ▪ Reference:

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Endosomal APPL (white) enters the nucleus after EGF treatment (right).Zerial/Elsevier
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uro1: Endosomal APPL (white) enters the nucleus after EGF treatment (right).Zerial/Elsevier


Endosomes are ready and APPL to signal
Endosomal APPL (white) enters the nucleus after EGF treatment (right).Zerial/Elsevier
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Related In: Results  -  Collection

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uro1: Endosomal APPL (white) enters the nucleus after EGF treatment (right).Zerial/Elsevier

View Article: PubMed Central

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Activation of Rab5 by binding of extracellular factors such as EGF to their receptors stimulates endocytosis... Zerial's group shows that some EGF-containing endosomes trigger nuclear responses via two newly identified Rab effectors, APPL1 and APPL2... Thus, EGF can elicit signal transduction cascades from both endosomes and the plasma membrane... The APPL proteins were found in a unique subset of Rab5- and EGF-containing endosomes... GTP hydrolysis by Rab5 then released APPLs from the membranes so that they could enter the nucleus... There, APPLs interacted with a histone deacetylase and chromatin-remodeling proteins that are needed for cell cycle progression—and thus EGF's proliferative effects... Loss of APPL or its interaction with Rab5 blocked DNA synthesis and cell proliferation... Besides EGF, oxidative stress also relocated APPLs to the nucleus, and the authors believe that other growth factors will have the same effect... Miaczynska is now interested in determining whether the APPL-containing membranes are simply transport vesicles, subcompartments of early endosomes, or bona fide organelles. “If an organelle linked to endocytosis exists that is dedicated to signaling, it would increase the possibilities of regulation in the cell,” says Zerial. “It would explain why different cells respond so differently to growth factors, because the amount of this pathway differs... In essence, the ability of a cell to respond to growth factors depends not only on the set of receptors and signaling molecules but also on their trafficking pathways. ” ▪ Reference:

No MeSH data available.