Protein transport to the dendritic plasma membrane of cultured neurons is regulated by rab8p.

Huber, Lukas A.; Hoop, M. J. De; Dupree, Paul; Zerial, Marino; Simons, Kai; Dotti, Carlos G.

doi:10.1083/jcb.123.1.47

Cited by 124 publications

(75 citation statements)

References 47 publications

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“…One hypothesis is suggested by the interaction between TRIP8b and Rab8b (S. . Although the specific function of Rab8b is not known, the closest relative of Rab8b, Rab8, is involved in polarized transport of vesicles to the plasma membrane of hippocampal neuron dendrites (Huber et al, 1993;Peranen et al, 1996). If this function were conserved in Rab8b, TRIP8b could participate in the transport of HCN channel proteins to the dendrites of pyramidal neurons, by mediating their association with Rab8b-linked vesicles.…”

Section: Role Of Trip8b In the Regulation Of Hcn Channel Expressionmentioning

confidence: 99%

Regulation of HCN Channel Surface Expression by a Novel C-Terminal Protein-Protein Interaction

Santoro

Wainger²,

Siegelbaum³

2004

J. Neurosci.

190

239

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Hyperpolarization-activated cation currents (I h ) are carried by channels encoded by a family of four genes (HCN1-4) that are differentially expressed within the brain in specific cellular and subcellular compartments. HCN1 shows a high level of expression in apical dendrites of cortical pyramidal neurons and in presynaptic terminals of cerebellar basket cells, structures with a high density of I h . Expression of I h is also regulated by neuronal activity. To isolate proteins that may control HCN channel expression or function, we performed yeast two-hybrid screens using the C-terminal cytoplasmic tails of the HCN proteins as bait. We identified a brain-specific protein, which has been previously termed TRIP8b (for TPR-containing Rab8b interacting protein) and PEX5Rp (for Pex5p-related protein), that specifically interacts with all four HCN channels through a conserved sequence in their C-terminal tails. In situ hybridization and immunohistochemistry show that TRIP8b and HCN1 are colocalized, particularly within dendritic arbors of hippocampal CA1 and neocortical layer V pyramidal neurons. The dendritic expression of TRIP8b in layer V pyramidal neurons is disrupted after deletion of HCN1 through homologous recombination, demonstrating a key in vivo interaction between HCN1 and TRIP8b. TRIP8b dramatically alters the trafficking of HCN channels heterologously expressed in Xenopus oocytes and human embryonic kidney 293 cells, causing a specific decrease in surface expression of HCN protein and I h density, with a pronounced intracellular accumulation of HCN protein that is colocalized in discrete cytoplasmic clusters with TRIP8b. Finally, TRIP8b expression in cultured pyramidal neurons markedly decreases native I h density. These data suggest a possible role for TRIP8b in regulating HCN channel density in the plasma membrane.

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Section: Role Of Trip8b In the Regulation Of Hcn Channel Expressionmentioning

confidence: 99%

Regulation of HCN Channel Surface Expression by a Novel C-Terminal Protein-Protein Interaction

Santoro

Wainger²,

Siegelbaum³

2004

J. Neurosci.

190

239

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“…The small GTP-binding protein Rab8 is reported to be involved in basolateral transport in epithelial cells (Huber et al, 1993a;Ang et al, 2003;Henry and Sheff, 2008) and in dendritic transport in neurons (Huber et al, 1993b). Rab8 is also reported to be involved in trafficking of neurotransmitter receptors in postsynaptic terminals (Gerges et al, 2004) and the formation of outer photoreceptor segments in the retina (Moritz et al, 2001;Bachmann-Gagescu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis

Satō¹,

Iwano²,

Kunii³

et al. 2014

Development

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The small GTP-binding protein Rab8 is known to play an essential role in intracellular transport and cilia formation. We have previously demonstrated that Rab8a is required for localising apical markers in various organisms. Rab8a has a closely related isoform, Rab8b. To determine whether Rab8b can compensate for Rab8a, we generated Rab8b-knockout mice. Although the Rab8b-knockout mice did not display an overt phenotype, Rab8a and Rab8b double-knockout mice exhibited mislocalisation of apical markers and died earlier than Rab8a-knockout mice. The apical markers accumulated in three intracellular patterns in the double-knockout mice. However, the localisation of basolateral and/or dendritic markers of the double-knockout mice seemed normal. The morphology and the length of various primary and/or motile cilia, and the frequency of ciliated cells appeared to be identical in control and double-knockout mice. However, an additional knockdown of Rab10 in double-knockout cells greatly reduced the percentage of ciliated cells. Our results highlight the compensatory effect of Rab8a and Rab8b in apical transport, and the complexity of the apical transport process. In addition, neither Rab8a nor Rab8b are required for basolateral and/or dendritic transport. However, simultaneous loss of Rab8a and Rab8b has little effect on ciliogenesis, whereas additional loss of Rab10 greatly affects ciliogenesis.

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Section: Introductionmentioning

confidence: 99%

“…Rab8 is known to regulate traffic along the TGN-RE-plasma membrane pathway, but whether this involves traffic into, through or out from the RE is not clear. Rab8 is also involved in AMPA recruitment to dendritic spines from the RE of neurons and thus may serve in both sorting and storage functions of the RE (Huber et al, 1993a;Gerges et al, 2004).Given the diverse roles of Rab8 in a variety of contexts, it could potentially act 1) in the transport of vesicles from the TGN to the RE, perhaps controlling fusion into the RE; 2) in organizing the sorting of basolateral traffic into subdomains of the RE as vesicular traffic enters this structure; or 3) in budding from the RE and delivery of cargo to the plasma membrane, including the penetration of the actin-filament web near the plasma membrane (Peranen et al, 1996;Hattula et al, 2002). In an effort to resolve these issues, we examined the requirement for Rab8 in the polarized sorting of endocytic ligands and secreted proteins in MDCK cells.…”

mentioning

confidence: 99%

Rab8 Regulates Basolateral Secretory, But Not Recycling, Traffic at the Recycling Endosome

Henry

Sheff

2008

MBoC

108

116

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Rab8 is a monomeric GTPase that regulates the delivery of newly synthesized proteins to the basolateral surface in polarized epithelial cells. Recent publications have demonstrated that basolateral proteins interacting with the 1-B clathrin adapter subunit pass through the recycling endosome (RE) en route from the TGN to the plasma membrane. Because Rab8 interacts with these basolateral proteins, these findings raise the question of whether Rab8 acts before, at, or after the RE. We find that Rab8 overexpression during the formation of polarity in MDCK cells, disrupts polarization of the cell, explaining how Rab8 mutants can disrupt basolateral endocytic and secretory traffic. However, once cells are polarized, Rab8 mutants cause mis-sorting of newly synthesized basolateral proteins such as VSV-G to the apical surface, but do not cause mis-sorting of membrane proteins already at the cell surface or in the endocytic recycling pathway. Enzymatic ablation of the RE also prevents traffic from the TGN from reaching the RE and similarly results in mis-sorting of newly synthesized VSV-G. We conclude that Rab8 regulates biosynthetic traffic through REs to the plasma membrane, but not trafficking of endocytic cargo through the RE. The data are consistent with a model in which Rab8 functions in regulating the delivery of TGN-derived cargo to REs. INTRODUCTIONThe Rab proteins are small monomeric GTPases of the Ras family. More than 60 known Rabs collectively regulate the flow of nearly all membrane traffic within the cell (Pfeffer, 1994;Gurkan et al., 2005;Jordens et al., 2005). Of these, mammalian Rab8 has been associated with the flow of newly synthesized proteins to the basolateral surface in polarized epithelial cells (Huber et al., 1993b;Moritz et al., 2001). In yeast, the Rab8 homolog, sec4, is also required for the targeting of membrane traffic to the plasma membrane (Guo et al., 1999). It has been suggested that Rab8 may be active in delivery of secretory cargo from the TGN to the plasma membrane. (Chen et al., 1993;Huber et al., 1993b). Studies of vesicular stomatitis virus protein G (VSV-G) delivery from the trans-Golgi network (TGN) have suggested that this process is regulated by Rab8, as dominant-negative (DN) mutants of Rab8 interfere with the delivery of basolateral cargo (Huber et al., 1993b). Rab8 is not localized to the TGN; rather it is localized at or near the recycling endosome (RE) in both polarized and nonpolarized cells (Hattula et al., 2006; Roland et al., 2007). The function of Rab8 at the RE is likely to regulate recycling of membrane traffic, although its role in polarized sorting is not clear. Rab8 is not required for the delivery of all basolateral proteins, but appears to be obligatory in the case of those that bear a tyrosine-dependent basolateral-sorting determinant capable of interacting with the clathrin adapter 1-B (Ang et al., 2003). The basolateral TGN-to-plasma membrane trafficking pathway is not as direct as once thought. Recent reports demonstrate clearly that 1-B-dependent basolater...

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Protein transport to the dendritic plasma membrane of cultured neurons is regulated by rab8p.

Abstract: Abstract. In the companion paper (Huber, L. A.,

Cited by 124 publications

References 47 publications

Regulation of HCN Channel Surface Expression by a Novel C-Terminal Protein-Protein Interaction

Regulation of HCN Channel Surface Expression by a Novel C-Terminal Protein-Protein Interaction

Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis

Rab8 Regulates Basolateral Secretory, But Not Recycling, Traffic at the Recycling Endosome

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