Structural Insights into Triglyceride Storage Mediated by Fat Storage-Inducing Transmembrane (FIT) Protein 2

Fat storage-Inducing Transmembrane proteins 1 & 2 (FIT1/FITM1 and FIT2/FITM2) belong to a unique family of evolutionarily conserved proteins localized to the endoplasmic reticulum that are involved in triglyceride lipid droplet formation. FIT proteins have been shown to mediate the partitioning of cellular triglyceride into lipid droplets, but not triglyceride biosynthesis. FIT proteins do not share primary sequence homology with known proteins and no structural information is available to inform on the mechanism by which FIT proteins function. Here, we present the experimentally-solved topological models for FIT1 and FIT2 using N-glycosylation site mapping and indirect immunofluorescence techniques. These methods indicate that both proteins have six-transmembrane-domains with both N- and C-termini localized to the cytosol. Utilizing this model for structure-function analysis, we identified and characterized a gain-of-function mutant of FIT2 (FLL(157-9)AAA) in transmembrane domain 4 that markedly augmented the total number and mean size of lipid droplets. Using limited-trypsin proteolysis we determined that the FLL(157-9)AAA mutant has enhanced trypsin cleavage at K86 relative to wild-type FIT2, indicating a conformational change. Taken together, these studies indicate that FIT2 is a 6 transmembrane domain-containing protein whose conformation likely regulates its activity in mediating lipid droplet formation

Beyond knowing nature: Contact, emotion, compassion, meaning, and beauty are pathways to nature connection

Feeling connected to nature has been shown to be beneficial to wellbeing and pro-environmental behaviour. General nature contact and knowledge based activities are often used in an attempt to engage people with nature. However the specific routes to nature connectedness have not been examined systematically. Two online surveys (total n = 321) of engagement with, and value of, nature activities structured around the nine values of the Biophila Hypothesis were conducted. Contact, emotion, meaning, and compassion, with the latter mediated by engagement with natural beauty, were predictors of connection with nature, yet knowledge based activities were not. In a third study (n = 72), a walking intervention with activities operationalising the identified predictors, was found to significantly increase connection to nature when compared to walking in nature alone or walking in and engaging with the built environment. The findings indicate that contact, emotion, meaning, compassion, and beauty are pathways for improving nature connectedness. The pathways also provide alternative values and frames to the traditional knowledge and identification routes often used by organisations when engaging the public with nature.N/