Bu, M. | bioRxiv Science

bioRxiv2023

CLAIR: An integrated lipid database across multiple crop species

Oilseed crops, which are rich in plant lipids, provide essential fatty acids for human consumption and serve as major sources of biofuels and essential raw materials for the chemical industry. As a result of population growth and ecological changes, the demand for vegetable oil is increasingly outpacing supply. A comprehensive understanding of the genes involved in lipid metabolism in oilseed crops and the regulatory relationships among these genes is essential for improving oil content. However, current studies on lipid metabolism genes rely heavily on a decade-old database of genes involved in lipid metabolism in Arabidopsis thaliana. To address this issue, we mined the literature, integrated data from various databases and studies, and aligned homologs of lipid metabolism genes from nine oilseed crops to construct a comprehensive set of lipid metabolism genes in plants. Using this approach, we identified 221 additional lipid metabolism genes. In addition, we created a user-friendly lipid database called CLAIR (Crop Lipid-Associated Information Resource) by integrating and mining multi-omics data from nine major oil crops. The database is available at http://www.clipair.cn/. These resources should facilitate further research and exploration of lipid metabolism in oil crops, ultimately contributing to improved oil production.

plant biology↗

bioRxiv2023

Inhibition of LRRK2 kinase activity rescues deficits in striatal dopamine dynamics in VPS35 p.D620N knock-in mice

Dysregulation of dopamine neurotransmission profoundly affects motor, motivation and learning behaviors, and is often observed during the prodromal phase of Parkinsons disease (PD). However, the mechanism underlying these pathophysiological changes remains to be elucidated. Mutations in vacuolar protein sorting 35 (VPS35) and leucine-rich repeat kinase 2 (LRRK2) both lead to autosomal dominant PD, and VPS35 and LRRK2 may physically interact to govern the trafficking of synaptic cargos within the endo-lysosomal network in a kinase-dependent manner. To better understand the functional role of VPS35 and LRRK2 on dopamine physiology, we examined Vps35 haploinsufficient (Haplo) and Vps35 p.D620N knock-in (VKI) mice and how their behavior, dopamine kinetics and biochemistry are influenced by LRRK2 kinase inhibitors. We found Vps35 p.D620N significantly elevates LRRK2-mediated phosphorylation of Rab10, Rab12 and Rab29. In contrast, Vps35 haploinsufficiency reduces phosphorylation of Rab12. While striatal dopamine transporter (DAT) expression and function is similarly impaired in both VKI and Haplo mice, that physiology is normalized in VKI by treatment with the LRRK2 kinase inhibitor, MLi-2. As a corollary, VKI animals show a significant increase in amphetamine induced hyperlocomotion, compared to Haplo mice, that is also abolished by MLi-2. Taken together, these data show Vps35 p.D620N confers a gain-of-function with respect to LRRK2 kinase activation, and VPS35 and LRRK2 functionally interact to regulate DAT trafficking and striatal dopamine neurotransmission.

neuroscience↗