Sequence-Dependent Sorting of Recycling Proteins by Actin-Stabilized Endosomal Microdomains

Puthenveedu, Manojkumar A.; Lauffer, Benjamin E.L.; Temkin, Paul; Vistein, Rachel; Carlton, Peter M.; Thorn, Kurt S.; Taunton, Jack; Weiner, Orion D.; Parton, Robert G.; Zastrow, Mark von

doi:10.1016/j.cell.2010.10.003

Cited by 297 publications

(415 citation statements)

References 56 publications

Supporting

Mentioning

386

Contrasting

Unclassified

Order By: Relevance

“…While still activating intracellular cAMP, Gαs DREADDs act as a 'generic' Gαs GPCR, it is currently unclear whether this tool exhibits identical intracellular signaling cascades comparable to the endogenous Gαs receptors expressed within the BLA. We now know, for instance, that all pools of Gαs are not identical and that receptors signal to G-proteins in a very selective microdomain-dependent manner that is limited by receptor subtype (Irannejad et al, 2013;Puthenveedu et al, 2010). Studies thoroughly comparing the pharmacodynamic properties of Gαs DREADDs to canonical GPCRs, such as β 2 AR, are needed to provide further validation.…”

Section: Discussionmentioning

confidence: 99%

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

Siuda

Al‐Hasani

McCall

et al. 2016

Neuropsychopharmacol

View full text Add to dashboard Cite

Anxiety disorders are debilitating psychiatric illnesses with detrimental effects on human health. These heightened states of arousal are often in the absence of obvious threatening cues and are difficult to treat owing to a lack of understanding of the neural circuitry and cellular machinery mediating these conditions. Activation of noradrenergic circuitry in the basolateral amygdala is thought to have a role in stress, fear, and anxiety, and the specific cell and receptor types responsible is an active area of investigation. Here we take advantage of two novel cellular approaches to dissect the contributions of G-protein signaling in acute and social anxiety-like states. We used a chemogenetic approach utilizing the Gαs DREADD (rM3Ds) receptor and show that selective activation of generic Gαs signaling is sufficient to induce acute and social anxiety-like behavioral states in mice. Second, we use a recently characterized chimeric receptor composed of rhodopsin and the β 2 -adrenergic receptor (Opto-β 2 AR) with in vivo optogenetic techniques to selectively activate Gαs β-adrenergic signaling exclusively within excitatory neurons of the basolateral amygdala. We found that optogenetic induction of β-adrenergic signaling in the basolateral amygdala is sufficient to induce acute and social anxiety-like behavior. These findings support the conclusion that activation of Gαs signaling in the basolateral amygdala has a role in anxiety. These data also suggest that acute and social anxiety-like states may be mediated through signaling pathways identical to β-adrenergic receptors, thus providing support that inhibition of this system may be an effective anxiolytic therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

Siuda

Al‐Hasani

McCall

et al. 2016

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…In recent years it has become apparent that retromer sorts cargo at multiple exit portals within the endosomal system, and our results suggest that multivalent interactions underlie localization of retromer at other exit sites. A candidate component of a mechanism to recruit retromer to the early endosome is SNX27, which is recognized by the VPS26 retromer subunit (26)(27)(28)(29), where it functions in a plasma membrane recycling pathway that is regulated by Rab4. Multivalent interactions allow diverse retromer recruitment mechanisms and can explain how retromer functions in organisms, such as Arabidopsis thaliana, which do not possess a SNX3 ortholog.…”

Section: Discussionmentioning

confidence: 99%

A mechanism for retromer endosomal coat complex assembly with cargo

Harrison

Hung

Liu

et al. 2013

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

145

172

View full text Add to dashboard Cite

Retromer is an evolutionarily conserved protein complex composed of the VPS26, VPS29, and VPS35 proteins that selects and packages cargo proteins into transport carriers that export cargo from the endosome. The mechanisms by which retromer is recruited to the endosome and captures cargo are unknown. We show that membrane recruitment of retromer is mediated by bivalent recognition of an effector of PI3K, SNX3, and the RAB7A GTPase, by the VPS35 retromer subunit. These bivalent interactions prime retromer to capture integral membrane cargo, which enhances membrane association of retromer and initiates cargo sorting. The role of RAB7A is severely impaired by a mutation, K157N, that causes Charcot-Marie-Tooth neuropathy 2B. The results elucidate minimal requirements for retromer assembly on the endosome membrane and reveal how PI3K and RAB signaling are coupled to initiate retromer-mediated cargo export.sorting nexin | mass spectrometry | biochemical reconstitution | proteoliposome

show abstract

“…Such actin polymerization has been proposed to increase local membrane tension and/or strain at lipid domain boundary regions (line tension), processes thought to promote membrane fission (69)(70)(71). Alternatively, actin polymerization has also been proposed to stabilize membrane buds or tubules, allowing time for cargo loading (73). CDC-42 is a known regulator of TOCA proteins in other processes, and could function, along with the CDC-42-interacting PAR proteins, to control the activity of the TOCA proteins during vesicle budding.…”

Section: Discussionmentioning

confidence: 99%

A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling

Bai

Grant

2015

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

View full text Add to dashboard Cite

Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1-positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42-associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling.retromer | endocytic recycling | endosome | toca | wave

show abstract

Sequence-Dependent Sorting of Recycling Proteins by Actin-Stabilized Endosomal Microdomains

Cited by 297 publications

References 56 publications

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

A mechanism for retromer endosomal coat complex assembly with cargo

A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling

Contact Info

Product

Resources

About