| 2007 |
SNX4, through its PX and BAR domains, associates with tubular and vesicular elements of early endosomes and the juxtanuclear endocytic recycling compartment (ERC). SNX4 suppression causes lysosomal degradation of the transferrin receptor (TfnR), establishing its role in endosomal sorting and recycling. SNX4 interacts with KIBRA (which binds dynein light chain 1) to associate with the minus-end-directed microtubule motor dynein, linking membrane tubulation-driven cargo sorting to long-range carrier transport from early endosomes to the ERC. |
siRNA knockdown, co-immunoprecipitation, fluorescence microscopy, endosomal fractionation |
Nature cell biology |
High |
17994011
|
| 2003 |
In yeast, Snx4p (ortholog of SNX4) mediates retrieval of the exocytic v-SNARE Snc1p from post-Golgi endosomes back to the Golgi. Snc1p can be chemically cross-linked to Snx4p. Snx4p physically binds Snx41p and Snx42p, and all three sorting nexins are required for efficient Snc1p sorting, defining a distinct retrieval pathway from early endosomes that is separable from the retromer pathway operating at pre-vacuolar endosomes. |
Chemical cross-linking, yeast genetics (deletion mutants), subcellular fractionation, fluorescence microscopy |
The EMBO journal |
High |
12554655
|
| 2009 |
SNX4 forms complexes with clathrin and dynein on endosomes; these interactions depend on PI3-kinase activity (inhibited by wortmannin), indicating they occur when SNX4 is PI(3)P-associated. A clathrin-box variant motif on SNX4 was identified as the clathrin-interacting site; a short peptide containing this motif is sufficient to pull down both clathrin and dynein. Clathrin knockdown is not required for the SNX4/dynein interaction but leads to increased retrograde Golgi transport of ricin and redistribution of endosomes, suggesting clathrin regulates SNX4-dependent transport. |
Co-immunoprecipitation, peptide pulldown, siRNA knockdown, pharmacological inhibition (wortmannin), fluorescence microscopy, toxin trafficking assay |
PloS one |
Medium |
19529763
|
| 2013 |
Reggie-1 (flotillin-2) directly interacts with SNX4 and Rab11a at the tubulovesicular recycling compartment. Reggie-1 depletion impairs TfR recycling to the plasma membrane and E-cadherin recycling after internalization; both defects are rescued by overexpression of constitutively active Rab11a or SNX4, placing reggie-1 as a regulator upstream of the Rab11a/SNX4-controlled recycling pathway. |
Co-immunoprecipitation (direct interaction), shRNA knockdown, overexpression rescue experiments, fluorescence microscopy |
Molecular biology of the cell |
Medium |
23825023
|
| 2017 |
Yeast Snx4 forms two functionally distinct heterodimers: Snx4-Atg20 and Snx4-Snx41. Each heterodimer coats a distinct endosome-derived tubule mediating retrograde sorting of different cargo: Snc1 is sorted by Snx4-Atg20, and Atg27 is sorted by Snx4-Snx41. The dynamin-family GTPase Vps1, which promotes fission of retromer-coated tubules, also promotes fission of Snx4-Atg20-coated tubules, linking tubule scission to Snx4-dependent retrograde trafficking. |
Live-cell fluorescence microscopy, genetic deletion, cargo-specific trafficking assays, co-localization |
Traffic (Copenhagen, Denmark) |
Medium |
28026081
|
| 2017 |
Yeast Snx4 cooperates with Snx41 and Snx42 to mediate autophagic turnover of the 26S proteasome and other large multisubunit complexes during nitrogen starvation. Snx4 is required for the formation of cytoplasmic proteasome puncta that accumulate when autophagosome formation is blocked, placing Snx4 at the step of cytoplasmic agglomeration of proteasomes prior to autophagic delivery. |
Yeast deletion mutants, fluorescence microscopy, pharmacological tethering, targeted autophagy gene screen |
The Journal of biological chemistry |
Medium |
29109144
|
| 2020 |
In mammalian cells, SNX4 is required for efficient LC3 lipidation and autophagosome assembly. SNX4 forms functional heterodimers with either SNX7 or SNX30 on tubulovesicular endocytic membranes. SNX4-SNX7 is an autophagy-specific heterodimer required for recruitment/retention of core autophagy regulators at the nascent isolation membrane. SNX4 partially co-localizes with juxtanuclear ATG9A-positive membranes, and SNX4 disruption causes mis-trafficking/retention of ATG9A in the Golgi region, linking the SNX4-SNX7 complex to ATG9A trafficking during autophagosome assembly. |
siRNA knockdown, CRISPR-Cas9 knockout, quantitative fluorescence microscopy, co-immunoprecipitation (heterodimer identification) |
Journal of cell science |
High |
32513819
|
| 2021 |
SNX4 mediates recycling of the lipid scramblase ATG9A from endolysosomes to early endosomes, from where ATG9A is further recycled to the trans-Golgi network in a retromer (VPS35)-dependent manner. SNX4 depletion causes accumulation of ATG9A on endolysosomes; VPS35 depletion causes accumulation on early endosomes. SNX4-mediated ATG9A recycling is required for starvation-induced autophagosome biogenesis and autophagic flux, likely by preventing exhaustion of the ATG9A pool. |
siRNA knockdown, fluorescence microscopy, autophagy flux assays |
Journal of cell science |
Medium |
33468622
|
| 2021 |
In yeast, the sorting nexin heterodimer Snx4/Atg24-Atg20 is required for a selective autophagy pathway (Snx4-assisted autophagy of transcription factors, SAA-TF) that targets transcriptional regulators Ssn2/Med13, Rim15, and Msn2 for vacuolar proteolysis upon nitrogen starvation. Snx4-Atg20 binds Atg17, relocates to the perinucleus upon starvation, and is required for efficient transfer of cargo (Ssn2/Med13) to Atg17-initiated phagophores anchored to the vacuole. |
Yeast genetics (deletion analysis), fluorescence microscopy, co-immunoprecipitation |
Autophagy |
Medium |
33678121
|
| 2024 |
In yeast, the Snx4-Atg20 heterodimer delivers the cargo Ssn2/Med13 to phagophores in the SAA-TF pathway. Ksp1, an autophagic receptor, is recruited early to phagophores via Atg29 independently of both Atg8 and Snx4; Snx4 delivers Ssn2/Med13 to phagophores thereafter, defining the temporal order of receptor and cargo delivery in this pathway. |
Yeast two-hybrid, genetic deletion analysis, fluorescence microscopy, mutagenesis of AIM/LIR motifs |
Autophagy |
Medium |
37733395
|
| 2024 |
In neurons, SNX4 conditional knockout leads to an increase in docked synaptic vesicles at the active zone and decreased active zone length, resulting in increased docked vesicle density per release site. This causes enhanced neurotransmission during train stimulation without affecting vesicle recycling, autophagic flux, or VAMP2/synaptobrevin-2 levels or localization, establishing SNX4 as a negative regulator of synaptic vesicle docking and release. |
Conditional knockout mouse model, electron microscopy (ultrastructure), electrophysiology (evoked EPSCs), Western blot, fluorescence microscopy |
eLife |
High |
39699951
|