Cephalopods are notable for their large
nervous systems and complex behaviors.
Progress in understanding the
underpinnings of these traits has been
limited by the lack of a genetically
tractable model. Using CRISPR, Ahuja
et al. generate albino lines of the squid
Euprymna berryi and then use them to
image neural activity in vivo.

Cook et al. carried out a screen and
identified a small molecule that can
promote bone formation, and determined
that it functions by activation of a specific
regulatory kinase, p38-b. This compound
is a promising candidate to develop a new
bone healing drug.

Activation of the unfolded protein response (UPR) can be either adaptive or pathological. We term the pathological UPR that causes fatty liver disease a “stressed UPR.” Here we investigate the mechanism of stressed UPR activation in zebrafish bearing a mutation in the trappc11 gene, which encodes a component of the transport protein particle (TRAPP) complex. trappc11 mutants are characterized by secretory pathway defects, reflecting disruption of the TRAPP complex. In addition, we uncover a defect in protein glycosylation in trappc11 mutants that is associated with reduced levels of lipid-linked oligosaccharides (LLOs) and compensatory up-regulation of genes in the terpenoid biosynthetic pathway that produces the LLO anchor dolichol. Treating wild-type larvae with terpenoid or LLO synthesis inhibitors phenocopies the stressed UPR seen in trappc11 mutants and is synthetically lethal with trappc11 mutation. We propose that reduced LLO level causing hypoglycosylation is a mechanism of stressed UPR induction in trappc11 mutants. Of importance, in human cells, depletion of TRAPPC11, but not other TRAPP components, causes protein hypoglycosylation, and lipid droplets accumulate in fibroblasts from patients with the TRAPPC11 mutation. These data point to a previously unanticipated and conserved role for TRAPPC11 in LLO biosynthesis and protein glycosylation in addition to its established function in vesicle trafficking.