Lysosomal targeting of phafin1 mediated by Rab7 induces autophagosome formation

Lin, Wen Jie; Yang, Chung‐May; Li, Li Li; Yi, Yung Hsiang; Chen, Kewei; Lin, Ying; Liu, Chin Chun; Lin, Chi

doi:10.1016/j.bbrc.2011.11.043

Cited by 27 publications

(26 citation statements)

References 36 publications

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“…We observed that DDK-Phafin2positive endosomes were early in their character (positive for Rab5, EEA1, HRS and TfR), and not characteristic of recycling endosomes (negative for Rab11), nor late endosomes (LBPA, Lamp1 and CD63 negative) ( Figure 8). This is in agreement with a published report using lysotracker as a late endocytic marker (31). It is well-known that proteins found on the same endosome can localize to different microdomains or 'hot-spots' in the limiting membrane of the endosome.…”

Section: Phafin2 Localizes To Eea1 and Rab5-positive Microdomains On supporting

confidence: 93%

“…Interestingly, in our screen, another member of the Phafin family, Phafin1, also affected EGF degradation, although not validated because of lack of relevant antibodies. Intriguingly, a recent report describes a function of Phafin1 in late endosomes and autophagosomes, and overexpression of Phafin1 gives rise to enlarged lysotracker‐positive late endosomes . Phafin2 and Phafin1 are therefore likely to both regulate EGFR degradation, Phafin1 possibly by working in late endosomal fusion and Phafin2 operating in early endosomal fusion as a novel member of the classical EEA1/Rab5 core fusion machinery.…”

Section: Discussionmentioning

confidence: 99%

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The PtdIns3P‐Binding Protein Phafin 2 Mediates Epidermal Growth Factor Receptor Degradation by Promoting Endosome Fusion

Pedersen

Raiborg

Brech

et al. 2012

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Phosphatidylinositol 3-phosphate (PtdIns3P) orchestrates endosomal cargo transport, fusion and motility by recruiting FYVE or PX domain-containing effector proteins to endosomal membranes. In an attempt to discover novel PtdIns3P effectors involved in the termination of growth factor receptor signalling, we performed an siRNA screen for epidermal growth factor (EGF) degradation, targeting FYVE and PX domain proteins in the human proteome. This screen identified several potential regulators of EGF degradation, including HRS (used as positive control), PX kinase, MTMR4 and Phafin2/PLEKHF2. As Phafin2 has not previously been shown to be required for EGF receptor (EGFR) degradation, we performed further functional studies on this protein. Loss of Phafin2 was found to decrease early endosome size, whereas overexpression of Phafin2 resulted in enlarged endosomes. Moreover, both the EGFR and the fluid-phase marker dextran were retained in abnormally small endosomes in Phafin2-depleted cells. In yeast two-hybrid analysis we identified Phafin2 as a novel interactor of the endosomal-tethering protein EEA1, and Phafin2 colocalized strongly with EEA1 in microdomains of the endosome membrane. Our results suggest that Phafin2 controls receptor trafficking and fluid-phase transport through early endosomes by facilitating endosome fusion in concert with EEA1.

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Section: Phafin2 Localizes To Eea1 and Rab5-positive Microdomains On supporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

The PtdIns3P‐Binding Protein Phafin 2 Mediates Epidermal Growth Factor Receptor Degradation by Promoting Endosome Fusion

Pedersen

Raiborg

Brech

et al. 2012

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“…Ras-related protein rab7 (RAB7A) harbored a 3'UTR SNP. RAB7A is a major regulator of endo-lysosomal maturation/ trafficking and protein targeting to lysosome inducing autophagosome formation [94].…”

Section: Unique Genes Affecting the Additive Genetic Variance For Moimentioning

confidence: 99%

Genome-Wide Scan for Common Variants Associated With Intramuscular Fat and Moisture Content in Rainbow Trout

Ali

Al-Tobasei

Lourenço³

et al. 2020

Preprint

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Background Genetic improvement of fillet quality attributes is a priority of the aquaculture industry. Muscle composition impacts quality attributes such as flavor, appearance, texture, and juiciness. Fat and moisture make up about ~80% of the tissue weight. The genetic architecture underlying the fat and moisture content of the muscle is still to be fully explored in fish. A 50K gene transcribed SNP chip was used for genotyping 789 fish with available phenotypic data for fat and moisture content. Genotyped fish were obtained from two consecutive generations produced in the National Center for Cool and Cold Water Aquaculture (NCCCWA) growth-selective breeding program. Estimates of SNP effects from weighted single-step GBLUP (WssGBLUP) were used to perform genome-wide association (GWA) analysis to identify quantitative trait loci (QTL) associated with the studied traits. Results Using genomic sliding windows of 50 adjacent SNPs, 137 and 178 SNPs were identified as associated with fat and moisture content, respectively. Chromosomes 19 and 29 harbored the highest number of SNPs explaining at least 2% of the genetic variation in fat and moisture content. A total of 61 common SNPs on chromosomes 19 and 29 affected the aforementioned traits; this association suggests common mechanisms underlying intramuscular fat and moisture content. Additionally, based on single-marker GWA analyses, 8 and 24 SNPs were identified in association with fat and moisture content, respectively. Conclusion SNP-harboring genes were primarily involved in lipid metabolism, cytoskeleton remodeling, and protein turnover. This work provides putative SNP markers that could be prioritized and used for genomic selection in breeding programs.

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“…Phafin2 regulates the function and structure of endosomes through a Rab5‐dependent process although no direct interaction of Phafin2 and Rab5 occurs . Several lines of evidence suggest that Phafin2, the Phafin family member protein Phafin1, and the Drosophila homologue Rush promote the enlargement of early endosomes with their FYVE domains playing a dominant role . Phafin2 interacts with the FYVE domain‐containing protein EEA1, which regulates endosomal cargo trafficking and fusion events, but does not directly participate in cargo sorting .…”

Section: Introductionmentioning

confidence: 99%

Structural, thermodynamic, and phosphatidylinositol 3‐phosphate binding properties of Phafin2

Tang

Deng

et al. 2017

Protein Science

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Phafin2 is a phosphatidylinositol 3‐phosphate (PtdIns(3)P) binding protein involved in the regulation of endosomal cargo trafficking and lysosomal induction of autophagy. Binding of Phafin2 to PtdIns(3)P is mediated by both its PH and FYVE domains. However, there are no studies on the structural basis, conformational stability, and lipid interactions of Phafin2 to better understand how this protein participates in signaling at the surface of endomembrane compartments. Here, we show that human Phafin2 is a moderately elongated monomer of ∼28 kDa with an intensity‐average hydrodynamic diameter of ∼7 nm. Circular dichroism (CD) analysis indicates that Phafin2 exhibits an α/β structure and predicts ∼40% random coil content in the protein. Heteronuclear NMR data indicates that a unique conformation of Phafin2 is present in solution and dispersion of resonances suggests that the protein exhibits random coiled regions, in agreement with the CD data. Phafin2 is stable, displaying a melting temperature of 48.4°C. The folding‐unfolding curves, obtained using urea‐ and guanidine hydrochloride‐mediated denaturation, indicate that Phafin2 undergoes a two‐state native‐to‐denatured transition. Analysis of these transitions shows that the free energy change for urea‐ and guanidine hydrochloride‐induced Phafin2 denaturation in water is ∼4 kcal mol−1. PtdIns(3)P binding to Phafin2 occurs with high affinity, triggering minor conformational changes in the protein. Taken together, these studies represent a platform for establishing the structural basis of Phafin2 molecular interactions and the role of the two potentially redundant PtdIns(3)P‐binding domains of the protein in endomembrane compartments.

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Lysosomal targeting of phafin1 mediated by Rab7 induces autophagosome formation

Cited by 27 publications

References 36 publications

The PtdIns3P‐Binding Protein Phafin 2 Mediates Epidermal Growth Factor Receptor Degradation by Promoting Endosome Fusion

The PtdIns3P‐Binding Protein Phafin 2 Mediates Epidermal Growth Factor Receptor Degradation by Promoting Endosome Fusion

Genome-Wide Scan for Common Variants Associated With Intramuscular Fat and Moisture Content in Rainbow Trout

Structural, thermodynamic, and phosphatidylinositol 3‐phosphate binding properties of Phafin2

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