The location where the isoform is most prominently activated thereby selectively affecting endosomal sorting and signaling events. Rab5A interacts more favorably with the Rab5 GEF, Rin1 when cells are stimulated with EGF. Rin1 interacts with the EGF- and other growth factor receptors through its SH2 domain thereby linking Rab5A activation with EGFR signaling. As mentioned above, Rab5C selectively interacts with AMAP suggesting that Rab5C may be recruited to the Arf6/ integrin pathway. It is also possible that Rab5C interacts with the exocyst, the macromolecular complex that regulates the activation of Rac1 and cell motility. A recent paper by Blumer and colleagues proposes that the interaction between Rabs and their exchange factors along with other Rab interacting proteins is responsible for controlling the targeting of individual Rabs to their appropriate localization. With the range of Rab5 GEFs currently cataloged and other Rab tethering factors such as EEA1, this could be the most attractive explanation for the selective targeting of the Rab5 isoforms to endosomal sub-compartments. Interestingly, Stenmark and colleagues reported many years ago that EEA1 preferentially interacts with Rab5B in a yeast two-hybrid screen suggesting that the activation of the various isoforms of Rab5 are variable. In summary, silencing of individual Rab5 isoforms showed distinct biological responses – suppression of Rab5A delays growth factor receptor trafficking while silencing of Rab5C suppresses Rac1 activation, cell shape, membrane ruffle formation and PI3K activity. We suggest that the Rab5 family WZ8040 1214265-57-2 evolved, along with any number of Rab5 effectors and activators, to orchestrate a “division of labor” to accommodate a more complicated endocytic pathway found in vertebrates. Impairment associated with depression is long-lasting and equal or greater than impairment caused by other common, chronic medical conditions such as diabetes, hypertension, heart attack, and congestive heart failure. Moreover, depression impairs functioning in various domains such as home life, workplace, friends, and family – severely compromising the capacity for self-care and independent living in many cases. A recent review found moderate correlations between scores on various screening instruments for depression and measures of impairment. It has been unclear, however, whether certain symptoms are more impairing than others, and if so, what the magnitude of these differences might be. This question is highly relevant because of large differences in the symptoms experienced by patients diagnosed with MDD. Qualifying for a diagnosis of MDD requires experiencing at least five of the nine DSM symptomatic criteria, among which at least one has to be either sad mood or loss of interest, for at least 2 weeks. Four symptoms are compound symptoms comprised by different subsymptoms or opposite subsymptoms, leading to 1,497 unique symptom profiles that all qualify for the same diagnosis, including profiles that do not have a single symptom in common. Considerable symptom variability has been reported across individuals and within individuals across time.