Unknown

Dataset Information

0

Trk-signaling endosomes are generated by Rac-dependent macroendocytosis.


ABSTRACT: Why neurotrophins and their Trk receptors promote neuronal differentiation and survival whereas receptor tyrosine kinases for other growth factors, such as EGF, do not, has been a long-standing question in neurobiology. We provide evidence that one difference lies in the selective ability of Trk to generate long-lived signaling endosomes. We show that Trk endocytosis is distinguished from the classical clathrin-based endocytosis of EGF receptor (EGFR). Although Trk and EGFR each stimulate membrane ruffling, only Trk undergoes both selective and specific macroendocytosis at ruffles, which uniquely requires the Rho-GTPase, Rac, and the trafficking protein, Pincher. This process leads to Trk-signaling endosomes, which are immature multivesicular bodies that retain Rab5. In contrast, EGFR endosomes rapidly exchange Rab5 for Rab7, thereby transiting into late-endosomes/lysosomes for degradation. Sustained endosomal signaling by Trk does not reflect intrinsic differences between Trk and EGFR, because each elicits long-term Erk-kinase activation from the cell surface. Thus, a population of stable Trk endosomes, formed by specialized macroendocytosis in neurons, provides a privileged endosome-based system for propagation of signals to the nucleus.

SUBMITTER: Valdez G 

PROVIDER: S-EPMC1941461 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Trk-signaling endosomes are generated by Rac-dependent macroendocytosis.

Valdez Gregorio G   Philippidou Polyxeni P   Rosenbaum Julie J   Akmentin Wendy W   Shao Yufang Y   Halegoua Simon S  

Proceedings of the National Academy of Sciences of the United States of America 20070717 30


Why neurotrophins and their Trk receptors promote neuronal differentiation and survival whereas receptor tyrosine kinases for other growth factors, such as EGF, do not, has been a long-standing question in neurobiology. We provide evidence that one difference lies in the selective ability of Trk to generate long-lived signaling endosomes. We show that Trk endocytosis is distinguished from the classical clathrin-based endocytosis of EGF receptor (EGFR). Although Trk and EGFR each stimulate membra  ...[more]

Similar Datasets

| S-EPMC3021064 | biostudies-literature
2019-11-06 | GSE122234 | GEO
| S-EPMC6368546 | biostudies-literature
| S-EPMC1462969 | biostudies-literature
| S-EPMC1965458 | biostudies-literature
| S-EPMC3666698 | biostudies-literature
| S-EPMC4177048 | biostudies-literature
| S-EPMC2872256 | biostudies-literature
| S-EPMC6726494 | biostudies-literature
| S-EPMC2842130 | biostudies-literature