A Lipid-TORC1 Pathway Promotes Neuronal Development and Foraging Behavior under Both Fed and Fasted Conditions in C. elegans.

Food deprivation suppresses animal growth and development but spares the systems essential for foraging. The mechanisms underlying this selective development, and potential roles of lipids in it, are unclear. When C. elegans hatch in a food-free environment, postembryonic growth and development stall, but sensory neuron differentiation and neuronal development required for food responses continue. Here, we show that monomethyl branched-chain fatty acids (mmBCFAs) and their derivative, d17iso-glucosylceramide, function in the intestine to promote foraging behavior and sensory neuron maturation through both TORC1-dependent and -independent mechanisms. We show that mmBCFAs impact the expression of a subset of genes, including ceh-36/Hox, which we show to play a key role in mediating the regulation of the neuronal functions by this lipid pathway. This study uncovers that a lipid pathway promotes neuronal functions involved in foraging under both fed and fasting conditions and adds critical insight into the physiological functions of TORC1.

Kniazeva M ，Zhu H ，Sewell AK ，Han M ... -  《-》

Intestinal apical polarity mediates regulation of TORC1 by glucosylceramide in C. elegans.

TORC1 (target of rapamycin complex 1) plays a central role in regulating growth, development, and behavior in response to nutrient cues. We previously showed that leucine-derived monomethyl branched-chain fatty acids (mmBCFAs) and derived glucosylceramide promote intestinal TORC1 activity for post-embryonic development and foraging behavior in Caenorhabditis elegans. Here we show that clathrin/adaptor protein 1 (AP-1)-dependent intestinal apical membrane polarity and polarity-dependent localization of the vacuolar-type H(+)-ATPase (V-ATPase) mediate the impact of the lipid pathway on intestinal TORC1 activation. Moreover, NPRL-3 represses mmBCFA-dependent intestinal TORC1 activity at least partly by regulating apical membrane polarity. Our results provide new insights into TORC1 regulation by lipids and membrane polarity in a specific tissue.

Zhu H ，Sewell AK ，Han M 《-》

A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans.

Zhu H ，Shen H ，Sewell AK ，Kniazeva M ，Han M ... -  《eLife》

Twists and turns--How we stepped into and had fun in the "boring" lipid field.

Han M 《-》

The intestinal TORC2 signaling pathway contributes to associative learning in Caenorhabditis elegans.

Sakai N ，Ohno H ，Tomioka M ，Iino Y ... -  《PLoS One》