EGF receptor trafficking: consequences for signaling and cancer

The ligand-stimulated epidermal growth factor receptor (EGFR) has been extensively studied in the analysis of molecular mechanisms regulating endocytic traffic and the role of that traffic in signal transduction. Although such studies have largely focused on mitogenic signaling and dysregulated traffic in tumorigenesis, there is growing interest in the potential role of EGFR traffic in cell survival and the consequent response to cancer therapy. Here we review recent advances in our understanding of molecular mechanisms regulating ligand-stimulated EGFR activation, internalization, and post-endocytic sorting. The role of EGFR overexpression/mutation and new modulators of EGFR traffic in cancer and the response to cancer therapeutics are also discussed. Finally, we speculate on the relationship between EGFR traffic and cell survival

Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles.

Multivesicular endosomes/bodies (MVBs) contain intraluminal vesicles (ILVs) that bud away from the cytoplasm. Multiple mechanisms of ILV formation have been identified, but the relationship between different populations of ILVs and MVBs remains unclear. Here, we show in HeLa cells that different ILV subpopulations can be distinguished by size. EGF stimulation promotes the formation of large ESCRT-dependent ILVs, whereas depletion of the ESCRT-0 component, Hrs, promotes the formation of a uniformly sized population of small ILVs, the formation of which requires CD63. CD63 has previously been implicated in ESCRT-independent sorting of PMEL in MVBs and transfected PMEL is present on the small ILVs that form on Hrs depletion. Upregulation of CD63-dependent ILV formation by Hrs depletion indicates that Hrs and CD63 regulate competing machineries required for the generation of distinct ILV subpopulations. Taken together our results indicate that ILV size is influenced by their cargo and mechanism of formation and suggest a competitive relationship between ESCRT-dependent and -independent mechanisms of ILV formation within single MVBs

Self-Rated Physical Attractiveness, Attractiveness Standards, and Expectation Deviations in Romantic Partners Among Non-Married University Students

This study surveyed unmarried, randomly selected university students to discover how they rated themselves regarding physical attractiveness, what range of attractiveness they would consider in a romantic partner, and what would cause them to deviate from this range. The results showed that the most frequently chosen rating for self-attractiveness was a 7 (on a scale of 1-10 with 10 being the most attractive) for both men and women. A t-test showed that men had a slightly higher mean of rating than women in their own level of attractiveness, though these results were not statistically significant. When asked for a range of attractiveness that respondents were willing to consider in a dating partner, the most frequently chosen number for the lowest level was 7. For the highest level of attractiveness in their range, about half of the participants selected 10. A t-test revealed that women had a slightly lower mean for the low end of the range of attractiveness they were willing to accept in a dating partner than males, which was statistically significant. Another t-test, though not statistically significant, revealed that men had a slightly higher mean in the high range of attractiveness they were willing to accept in a dating partner than women. Perhaps the most interesting finding was that not only were both genders willing to deviate from their standard of attractiveness in a dating partner (given the right circumstances), but women were much more likely to deviate than men

Self-Rated Physical Attractiveness, Attractiveness Standards, and Expectation Deviations in Romantic Partners Among Non-Married University Students

This study surveyed unmarried, randomly selected university students to discover how they rated themselves regarding physical attractiveness, what range of attractiveness they would consider in a romantic partner, and what would cause them to deviate from this range. The results showed that the most frequently chosen rating for self-attractiveness was a 7 (on a scale of 1-10 with 10 being the most attractive) for both men and women. A t-test showed that men had a slightly higher mean of rating than women in their own level of attractiveness, though these results were not statistically significant. When asked for a range of attractiveness that respondents were willing to consider in a dating partner, the most frequently chosen number for the lowest level was 7. For the highest level of attractiveness in their range, about half of the participants selected 10. A t-test revealed that women had a slightly lower mean for the low end of the range of attractiveness they were willing to accept in a dating partner than males, which was statistically significant. Another t-test, though not statistically significant, revealed that men had a slightly higher mean in the high range of attractiveness they were willing to accept in a dating partner than women. Perhaps the most interesting finding was that not only were both genders willing to deviate from their standard of attractiveness in a dating partner (given the right circumstances), but women were much more likely to deviate than men

Exploiting Connections for Viral Replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the COVID-19 (coronavirus disease 2019) pandemic, is a positive strand RNA (+RNA) virus. Like other +RNA viruses, SARS-CoV-2 is dependent on host cell metabolic machinery to survive and replicate, remodeling cellular membranes to generate sites of viral replication. Viral RNA-containing double-membrane vesicles (DMVs) are a striking feature of +RNA viral replication and are abundant in SARS-CoV-2-infected cells. Their generation involves rewiring of host lipid metabolism, including lipid biosynthetic pathways. Viruses can also redirect lipids from host cell organelles; lipid exchange at membrane contact sites, where the membranes of adjacent organelles are in close apposition, has been implicated in the replication of several +RNA viruses. Here we review current understanding of DMV biogenesis. With a focus on the exploitation of contact site machinery by +RNA viruses to generate replication organelles, we discuss evidence that similar mechanisms support SARS-CoV-2 replication, protecting its RNA from the host cell immune response

Cholesterol overload: contact sites to the rescue!

Delivery of low-density lipoprotein-derived cholesterol to the endoplasmic reticulum (ER) is essential for cholesterol homeostasis, yet the mechanism of this transport has largely remained elusive. Two recent reports shed some light on this process, uncovering a role for Niemann Pick type-C1 protein (NPC1) in the formation of membrane contact sites (MCS) between late endosomes (LE)/lysosomes (Lys) and the ER. Both studies identified a loss of MCS in cells lacking functional NPC1, where cholesterol accumulates in late endocytic organelles. Remarkably, and taking different approaches, both studies have made a striking observation that expansion of LE/Lys-ER MCS can rescue the cholesterol accumulation phenotype in NPC1 mutant or deficient cells. In both cases, the cholesterol was shown to be transported to the ER, demonstrating the importance of ER-LE/Lys contact sites in the direct transport of low-density lipoprotein-derived cholesterol to the ER

Exploiting Connections for Viral Replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the COVID-19 (coronavirus disease 2019) pandemic, is a positive strand RNA (+RNA) virus. Like other +RNA viruses, SARS-CoV-2 is dependent on host cell metabolic machinery to survive and replicate, remodeling cellular membranes to generate sites of viral replication. Viral RNA-containing double-membrane vesicles (DMVs) are a striking feature of +RNA viral replication and are abundant in SARS-CoV-2-infected cells. Their generation involves rewiring of host lipid metabolism, including lipid biosynthetic pathways. Viruses can also redirect lipids from host cell organelles; lipid exchange at membrane contact sites, where the membranes of adjacent organelles are in close apposition, has been implicated in the replication of several +RNA viruses. Here we review current understanding of DMV biogenesis. With a focus on the exploitation of contact site machinery by +RNA viruses to generate replication organelles, we discuss evidence that similar mechanisms support SARS-CoV-2 replication, protecting its RNA from the host cell immune response

Banner News

https://openspace.dmacc.edu/banner_news/1200/thumbnail.jp

The concluding chapter: Recircumscription of Goodenia (Goodeniaceae) to include four allied genera with an updated infrageneric classification

© 2020. Close scrutiny of Goodenia (Goodeniaceae) and allied genera in the \u27Core Goodeniaceae\u27 over recent years has clarified our understanding of this captivating group. While expanded sampling, sequencing of multiple regions, and a genome skimming reinforced backbone clearly supported Goodenia s.l. as monophyletic and distinct from Scaevola and Coopernookia, there appears to be no synapomorphic characters that uniquely characterise this morphologically diverse clade. Within Goodenia s.l., there is strong support from nuclear, chloroplast and mitochondrial data for three major clades (Goodenia Clades A, B and C) and various subclades, which lead to earlier suggestions for the possible recognition of these as distinct genera. Through ongoing work, it has become evident that this is impractical, as conflict remains within the most recently diverged Clade C, likely due to recent radiation and incomplete lineage sorting. In light of this, it is proposed that a combination of morphological characters is used to circumscribe an expanded Goodenia that now includes Velleia, Verreauxia, Selliera and Pentaptilon, and an updated infrageneric classification is proposed to accommodate monophyletic subclades. A total of twenty-five new combinations, three reinstatements, and seven new names are published herein including Goodenia subg. Monochila sect. Monochila subsect. Infracta K.A. Sheph. subsect. nov. Also, a type is designated for Goodenia subg. Porphyranthus sect. Ebracteolatae (K. Krause) K.A. Sheph. comb. et stat. nov., and lectotypes or secondstep lectotypes are designated for a further three names