Thank ORP9 for FFAT: With endosomal ORP10, it’s fission accomplished!

Heterogeneity in endosomal membrane phospholipid content is emerging as a regulator of endocytic trafficking pathways. Kawasaki et al. (2021. J. Cell. Biol.https://doi.org/10.1083/jcb.202103141) demonstrate exchange of endosomal PI4P for PS by ORP10 at ER–endosome contact sites, with the consequent recruitment of endosomal fission factors.

PSVI-29 Late-Breaking: Exposure to 1.8 mM choline chloride does not impact development to the blastocyst stage or pregnancy rate after transfer for embryos produced in vitro

Choline is a nutrient that plays a role as a precursor for the neurotransmitter acetylcholine, the membrane phospholipid phosphatidylcholine, and the methyl donor betaine. Embryos produced in vitro are usually cultured without an exogenous choline source. We hypothesized that exposure to 1.8 mM choline chloride would increase percent of embryos becoming blastocysts in culture and pregnancy rate after transfer of embryos into recipients. A total of 39 Brahman and Senepol donors were used to produce embryos for transfer into recipient crossbred females. Donors were assigned to have their embryos cultured in either 1.8 mM choline chloride or, as a control, 1.8 mM extra NaCl. The percent of oocytes cleaved were measured 3 days after insemination and percent blastocyst at day 7.5. Embryos were transferred into recipient cows and pregnancy was diagnosed at 28–31 days of gestation and then confirmed at 50–56 days. Data were analyzed using PROC GLIMMIX in SAS. Treatment did not affect cleavage rate (67.3 + 1.6 vs 68.6 + 1.6% for choline vs control; P = .0.5632) or percent of cleaved embryos becoming blastocysts (17.6 + 1.3 vs 18.1 + 1.3%; P = 0.5355). Similarly, there was no effect of treatment on pregnancy days 28–31 [42.5% (48/113 cows) vs 47.3% (54/114 cows) for choline vs control; P = 0.4339] or at days 50–56 [39.1% (36/92) vs 38.5% (32/83); P = 0.5348]. In summary, 1.8 mM choline chloride does not impact embryo development to the blastocyst stage or pregnancy establishment. Further investigation is needed to evaluate the phenotype of the subsequent calves to determine whether early exposure to choline has consequences for postnatal function. Support: USDA-NIFA 2020-67015-30821.

The binding of autotaxin to integrins mediates hyperhomocysteinemia-potentiated platelet activation and thrombosis

Hyperhomocysteinemia (HHcy) is associated with an exaggerated platelet thrombotic response at sites of vascular injury. Here, a human medical examination report showed that elevated human plasma Hcy levels were positively correlated with enhanced blood coagulation and platelet activity, suggesting that humans with HHcy are more prone to thrombus formation at the sites of vascular injury. Accordingly, we observed accelerated platelet activation, primary hemostasis, and thrombus formation both in acute and chronic HHcy ApoE-/- mice. Upon Hcy administration in C57BL/6J mice, platelet aggregation, spreading, and clot retraction were markedly promoted. More importantly, homocysteine (Hcy) increased the affinity of platelet integrin αIIbβ3 with ligands and enhanced integrin outside-in signaling by promoting membrane phosphatidylserine (PS) exposure in vitro. Mechanistically, lipidomics analysis showed that lysophosphatidylcholines were the primary metabolites leading to clustering of HHcy-stimulated platelets. Cytosolic phospholipase A2 (cPLA2) activity and autotaxin (ATX, a secreted lysophospholipase D) secretion were upregulated by Hcy, leading to membrane phospholipid hydrolysis and PS exposure. Moreover, secreted ATX directly interacted with integrin β3. Inhibitors of cPLA2 and ATX activity blocked integrin αIIbβ3 outside-in signaling and thrombosis in HHcy ApoE-/- mice. This study identifies a novel mechanism by which HHcy promotes platelet membrane phospholipid catabolism and extracellular ATX secretion to activate integrin outside-in signaling, consequently to exaggerate thrombosis. This study reveals an innovative approach to treat HHcy-related thrombotic diseases.

An Emerging Role for Phosphoinositides in the Pathophysiology of Parkinson’s Disease

Recent data support an involvement of defects in homeostasis of phosphoinositides (PIPs) in the pathophysiology of Parkinson’s disease (PD). Genetic mutations have been identified in genes encoding for PIP-regulating and PIP-interacting proteins, that are associated with familial and sporadic PD. Many of these proteins are implicated in vesicular membrane trafficking, mechanisms that were recently highlighted for their close associations with PD. PIPs are phosphorylated forms of the membrane phospholipid, phosphatidylinositol. Their composition in the vesicle’s membrane of origin, as well as membrane of destination, controls vesicular membrane trafficking. We review the converging evidence that points to the involvement of PIPs in PD. The review describes PD- and PIP-associated proteins implicated in clathrin-mediated endocytosis and autophagy, and highlights the involvement of α-synuclein in these mechanisms.

The phospholipid membrane compositions of bacterial cells, cancer cell lines and biological samples from cancer patients

This review acts as a repository and comparison of cell membrane phospholipid composition data collected from microbial and cancer fields.