The involvement of the small GTP-binding protein Rab5a in neuronal endocytosis

Hoop, M. J. De; Huber, Lukas A.; Stenmark, Harald; Williamson, Edward K.; Zerial, Marino; Parton, Robert G.; Dotti, Carlos G.

doi:10.1016/0896-6273(94)90456-1

Cited by 141 publications

(128 citation statements)

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“…To further demonstrate that EEA1 is undetectable on bona fide presynaptic endosomes, mature neurons were double labeled for Rab5 and EEA1 (Figure 5, E-G). Previous studies have shown that Rab5 is associated with both presynaptic and somatodendritic endosomes in rat hippocampal neurons (de Hoop et al, 1994). Consistent with these results, EEA1 and Rab5 colocalized on large punctate structures within dendrites ( Figure 5, small arrows).…”

Section: Polarized Distribution Of Eea1supporting

confidence: 78%

“…Synaptosomes were prepared from rat brain, and the relative levels of a presynaptic marker (synaptophysin), a postsynaptic marker (MAP2; Dotti et al, 1988), and EEA1 (detected with two different antisera) were determined during the purification. Under these purification conditions, the resealed synaptosomes retain peripheral membrane components (de Hoop et al, 1994) and remain functional (Takei et al, 1996). As shown in Figure 6, purification of synaptosomes was accompanied by enrichment of synaptophysin but depletion of MAP2.…”

Section: Polarized Distribution Of Eea1mentioning

confidence: 86%

“…We examined the distribution of EEA1 in polarized hippocampal neurons in which the axonal and somatodendritic endosomal populations are well separated (Parton and Dotti, 1993). Previous studies have shown that the axonal and somatodendritic domains of polarized rat hippocampal neurons possess distinct endocytic circuits (Parton et al, 1992) but that they share common components of the endocytic machinery, such as the small GTPase Rab5 (de Hoop et al, 1994).We first examined whether, as in fibroblasts, EEA1 is restricted to the early endosomal system. Double-labeling experiments showed that EEA1 colocalized with the early endosomal marker internalized rhodamine transferrin but not with the late endosomal/lysosomal marker LAMP1 (our unpublished results).…”

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confidence: 99%

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EEA1, a Tethering Protein of the Early Sorting Endosome, Shows a Polarized Distribution in Hippocampal Neurons, Epithelial Cells, and Fibroblasts

Wilson

Hoop

Zorzi

et al. 2000

MBoC

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180

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EEA1 is an early endosomal Rab5 effector protein that has been implicated in the docking of incoming endocytic vesicles before fusion with early endosomes. Because of the presence of complex endosomal pathways in polarized and nonpolarized cells, we have examined the distribution of EEA1 in diverse cell types. Ultrastructural analysis demonstrates that EEA1 is present on a subdomain of the early sorting endosome but not on clathrin-coated vesicles, consistent with a role in providing directionality to early endosomal fusion. Furthermore, EEA1 is associated with filamentous material that extends from the cytoplasmic surface of the endosomal domain, which is also consistent with a tethering/docking role for EEA1. In polarized cells (Madin-Darby canine kidney cells and hippocampal neurons), EEA1 is present on a subset of "basolateral-type" endosomal compartments, suggesting that EEA1 regulates specific endocytic pathways. In both epithelial cells and fibroblastic cells, EEA1 and a transfected apical endosomal marker, endotubin, label distinct endosomal populations. Hence, there are at least two distinct sets of early endosomes in polarized and nonpolarized mammalian cells. EEA1 could provide specificity and directionality to fusion events occurring in a subset of these endosomes in polarized and nonpolarized cells. INTRODUCTIONAnimal cells are continuously internalizing proteins and lipids of their plasma membrane via endocytosis. The internalized surface components enter a complex and dynamic membrane system, the early endosome, which plays a vital role in sorting endocytosed proteins to different destinations in the cell (Gruenberg and Maxfield, 1995). It is now clear that the early endosome comprises at least two functionally distinct compartments or subdomains (Ghosh et al., 1994;Ghosh and Maxfield, 1995;Gruenberg and Maxfield, 1995;Ullrich et al., 1996;Zacchi et al., 1998). Markers first enter the early sorting endosome, a complex organelle with tubular and multivesicular domains, where membrane proteins destined for degradation are sorted away from those proteins, such as the transferrin receptor, that are recycled back to the plasma membrane. Recycling proteins can then enter a second subcompartment, termed the recycling endosome, which has a tubular morphology and in many cell types is located in the pericentriolar area of the cell (Yamashiro et al., 1984;Dunn et al., 1989;Ghosh and Maxfield, 1995). Further complexity is added to this picture by the finding that fibroblasts, generally regarded as nonpolarized cells, may contain two sets of early endosomes analogous to those in polarized cells (Wilson and Colton, 1997). In these studies, endotubin, a membrane protein of the apical early endosomal compartment in neonatal rat intestine (Wilson et al., 1987), was heterologously expressed in normal rat kidney (NRK) cells and shown to associate with an apparently unique early endosomal compartment. This compartment was distinct from transferrin-containing early endosomes and was relatively insensitive to brefeldi...

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Section: Polarized Distribution Of Eea1supporting

confidence: 78%

Section: Polarized Distribution Of Eea1mentioning

confidence: 86%

mentioning

confidence: 99%

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EEA1, a Tethering Protein of the Early Sorting Endosome, Shows a Polarized Distribution in Hippocampal Neurons, Epithelial Cells, and Fibroblasts

Wilson

Hoop

Zorzi

et al. 2000

MBoC

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180

153

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“…Small GTPbinding proteins, such as Rab5a, have been shown to be involved in the regulation of neuronal endocytosis (de Hoop et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

A role of the tuberous sclerosis gene-2 product during neuronal differentiation

et al. 1998

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Tuberous sclerosis is an autosomal dominant disorder. Besides the development of benign growths (hamartomas) in di erent tissues, one hallmark of this disease is the presence of highly epileptogenic dysplastic lesions in the cerebral cortex (tubers) composed of abnormal shaped neurones. Patients often show evidence of severe mental retardation. Linkage analysis revealed two diseasedetermining genes on chromosome 9 and chromosome 16. The TSC2 gene on chromosome 16 encodes a 1784-amino acid putative tumour suppressor protein, tuberin, that functions as a GTPase-activating protein. Here we show that tuberin expression is upregulated upon induction of neuronal di erentiation in the neuroblastoma cell lines SK-N-SH and LAN-1. This upregulation occurs at post-transcriptional level and is independent of the proliferation status. TSC2 expression is una ected during di erentiation of C2C12 myoblasts into myotubes and of F9 embryonal carcinoma cells into cells resembling parietal endoderm. Antisense inhibition of tuberin expression in SK-N-SH or LAN-1 cells inhibits neuronal di erentiation, but does not a ect the di erentiation of F9 cells. Ectopic overexpression of TSC2 not only reverts the antisense-associated phenotype but furthermore accelerates the neuronal di erentiation process. Our data show for the ®rst time that tuberin plays a critical role in neuronal di erentiation. Such role is consistent with the phenotype of tuberous sclerosis patients, who inherit one defective TSC2 allele, and frequently lose the remaining normal allele in many of the tubers/hamartomas which develop in the central nervous system of these patients.

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“…One way by which cellular protrusions convey instructive cues is by endocytosis and trafficking of signaling complexes on endosomes. The early endosomal protein Rab5a localizes, for example, to axons and dendrites of neurons (de Hoop et al, 1994) and is important for coupling clathrin-dependent endocytosis to axonal retrograde transport (Deinhardt et al, 2006). Furthermore, several signaling molecules are associated with endosomes (reviewed in Miaczynska et al, 2004).…”

Section: Apical and Lateral Protrusions And Intercellular Signalingmentioning

confidence: 99%

Apical and lateral cell protrusions interconnect epithelial cells in live Drosophila wing imaginal discs

Demontis

Dahmann

2007

Developmental Dynamics

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The involvement of the small GTP-binding protein Rab5a in neuronal endocytosis

Cited by 141 publications

References 56 publications

EEA1, a Tethering Protein of the Early Sorting Endosome, Shows a Polarized Distribution in Hippocampal Neurons, Epithelial Cells, and Fibroblasts

EEA1, a Tethering Protein of the Early Sorting Endosome, Shows a Polarized Distribution in Hippocampal Neurons, Epithelial Cells, and Fibroblasts

A role of the tuberous sclerosis gene-2 product during neuronal differentiation

Apical and lateral cell protrusions interconnect epithelial cells in live Drosophila wing imaginal discs

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