Co-assembly of Viral Envelope Glycoproteins Regulates Their Polarized Sorting in Neurons

Mattera, Rafael; Farı́as, Ginny G.; Mardones, Gonzalo A.; Bonifacino, Juan S.

doi:10.1371/journal.ppat.1004107

Cited by 25 publications

(41 citation statements)

References 57 publications

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“…These observations indicated that the differential distribution of various cytoplasmic organelles between the somatodendritic and axonal domains (Raine, 1999) is established at the level of the PAEZ. The clathrin-associated AP-1 complex involved in cargo sorting into somatodendritic vesicles (Dwyer et al, 2001; Margeta et al, 2009; Farías et al, 2012; Mattera et al, 2014; Jain et al, 2015) was also excluded at the PAEZ, but the homologous AP-2 complex involved in endocytosis at both pre- and post-synaptic sites (Maycox et al, 1992; Lavezzari et al, 2003) was not excluded (Figure 4A). Filamentous actin was present, but not particularly concentrated, at the PAEZ and AIS (Figures 4A and S2), in line with recent observations (Jones et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

Sorting of Dendritic and Axonal Vesicles at the Pre-axonal Exclusion Zone

et al. 2015

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Summary Polarized sorting of newly-synthesized proteins to the somatodendritic and axonal domains of neurons occurs by selective incorporation into distinct populations of vesicular transport carriers. An unresolved issue is how the vesicles themselves become sorted to their corresponding neuronal domains. Previous studies concluded that the axon initial segment (AIS) is an actin-based filter that selectively prevents passage of somatodendritic vesicles into the axon. We find, however, that most somatodendritic vesicles fail to enter the axon at a more proximal region in the axon hillock herein referred to as the “pre-axonal exclusion zone” (PAEZ). Forced coupling of a somatodendritic cargo protein to an axonally-directed kinesin is sufficient to drive transport of whole somatodendritic vesicles through the PAEZ toward the distal axon. Based on these findings, we propose that polarized sorting of transport vesicles occurs at the PAEZ and depends on the ability of the vesicles to acquire an appropriately directed microtubule motor.

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Section: Resultsmentioning

confidence: 99%

Sorting of Dendritic and Axonal Vesicles at the Pre-axonal Exclusion Zone

et al. 2015

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“…The tyrosine-based motif 525 YSRL 528 is important for F protein endocytosis, and mutation of residue Y525 alters internalization of the protein (20,22). Recent work has also shown that mutation of residues Y525 and L528 results in a nonpolarized distribution of NiV F in neurons through disruption of the interaction with clathrin adaptor complex 1 (AP-1) components (47). The HeV F Y525A protein exhibited higher levels of cell surface expression than the wt F protein, leading to enhanced syncytium formation (Fig.…”

Section: Discussionmentioning

confidence: 99%

Mutations in the Transmembrane Domain and Cytoplasmic Tail of Hendra Virus Fusion Protein Disrupt Virus-Like-Particle Assembly

Cifuentes-Muñoz

Sun

Ray

et al. 2017

J Virol

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Hendra virus (HeV) is a zoonotic paramyxovirus that causes deadly illness in horses and humans. An intriguing feature of HeV is the utilization of endosomal protease for activation of the viral fusion protein (F). Here we investigated how endosomal F trafficking affects HeV assembly. We found that the HeV matrix (M) and F proteins each induced particle release when they were expressed alone but that their coexpression led to coordinated assembly of virus-like particles (VLPs) that were morphologically and physically distinct from M-only or F-only VLPs. Mutations to the F protein transmembrane domain or cytoplasmic tail that disrupted endocytic trafficking led to failure of F to function with M for VLP assembly. Wild-type F functioned normally for VLP assembly even when its cleavage was prevented with a cathepsin inhibitor, indicating that it is endocytic F trafficking that is important for VLP assembly, not proteolytic F cleavage. Under specific conditions of reduced M expression, we found that M could no longer induce significant VLP release but retained the ability to be incorporated as a passenger into F-driven VLPs, provided that the F protein was competent for endocytic trafficking. The F and M proteins were both found to traffic through Rab11-positive recycling endosomes (REs), suggesting a model in which F and M trafficking pathways converge at REs, enabling these proteins to preassemble before arriving at plasma membrane budding sites.IMPORTANCE Hendra virus and Nipah virus are zoonotic paramyxoviruses that cause lethal infections in humans. Unlike that for most paramyxoviruses, activation of the henipavirus fusion protein occurs in recycling endosomal compartments. In this study, we demonstrate that the unique endocytic trafficking pathway of Hendra virus F protein is required for proper viral assembly and particle release. These results advance our basic understanding of the henipavirus assembly process and provide a novel model for the interplay between glycoprotein trafficking and paramyxovirus assembly.

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“…In some cases this process is mediated by recognition of sorting signals in the cytosolic tails of the proteins by components of protein coats associated with the cytosolic face of the donor compartment. One of the best-documented examples is the sorting of various transmembrane proteins to the somatodendritic domain, which depends on interaction of tyrosine-based, dileucine-based, or noncanonical signals in the cytosolic domains of the proteins with the clathrin-associated adaptor protein 1 (AP-1) complex (6,13,(18)(19)(20) or the non-clathrin-associated AP-4 complex (21, 22). After the proteins are packaged into distinct transport carriers, the carriers themselves must be delivered to their corresponding neuronal domains, a process that is driven largely by interaction with specific microtubule motors (23,24).…”

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Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon

Guo

Farı́as

Mattera

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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An open question in cell biology is how the general intracellular transport machinery is adapted to perform specialized functions in polarized cells such as neurons. Here we illustrate this adaptation by elucidating a role for the ubiquitous small GTPase Ras-related protein in brain 5 (Rab5) in neuronal polarity. We show that inactivation or depletion of Rab5 in rat hippocampal neurons abrogates the somatodendritic polarity of the transferrin receptor and several glutamate receptor types, resulting in their appearance in the axon. This loss of polarity is not caused primarily by increased transport from the soma to the axon but rather by decreased retrieval from the axon to the soma. Retrieval is also dependent on the Rab5 effector Fused Toes (FTS)-Hook-FTS and Hook-interacting protein (FHIP) (FHF) complex, which interacts with the minus-enddirected microtubule motor dynein and its activator dynactin to drive a population of axonal retrograde carriers containing somatodendritic proteins toward the soma. These findings emphasize the importance of both biosynthetic sorting and axonal retrieval for the polarized distribution of somatodendritic receptors at steady state.Rab5 | FHF complex | dynein | neuronal polarity | retrograde transport N eurons are highly polarized cells with distinct somatodendritic and axonal domains. Synaptic inputs are received through the somatodendritic domain, integrated at the axon initial segment (AIS), and propagated along the axon for transmission to downstream cells. To accomplish these specialized functions, each neuronal domain is endowed with a distinct set of proteins. A fundamental but still largely unanswered question is how neurons establish and maintain this polarized distribution of proteins throughout their lifetimes. The available evidence indicates that the mechanisms of polarized sorting in neurons are quite complex (1-3). Newly synthesized transmembrane proteins travel together from their site of synthesis in the rough endoplasmic reticulum (ER) to the Golgi complex. Once they reach the trans-Golgi network (TGN), the proteins are sorted into different membraneenclosed transport carriers destined for the somatodendritic or axonal domains (4-8). However, the efficiency of this biosynthetic sorting varies for different proteins and is often incomplete. Other processes, such as compartment-specific retention, retrieval, or transcytosis, additionally contribute to establishing the overall distribution of proteins between the somatodendritic and axonal domains and to their localization to specialized subdomains (5, 9-17).The selective incorporation of transmembrane proteins into specialized transport carriers is a key event in the mechanisms of polarized sorting. In some cases this process is mediated by recognition of sorting signals in the cytosolic tails of the proteins by components of protein coats associated with the cytosolic face of the donor compartment. One of the best-documented examples is the sorting of various transmembrane proteins to the somatodendritic domain...

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Co-assembly of Viral Envelope Glycoproteins Regulates Their Polarized Sorting in Neurons

Cited by 25 publications

References 57 publications

Sorting of Dendritic and Axonal Vesicles at the Pre-axonal Exclusion Zone

Sorting of Dendritic and Axonal Vesicles at the Pre-axonal Exclusion Zone

Mutations in the Transmembrane Domain and Cytoplasmic Tail of Hendra Virus Fusion Protein Disrupt Virus-Like-Particle Assembly

Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon

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