Tu-Sekine Becky, Goldschmidt Hana, Raben Daniel M
The Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
The Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Adv Biol Regul. 2015 Jan;57:147-52. doi: 10.1016/j.jbior.2014.09.010. Epub 2014 Sep 28.
The synaptic vesicle (SV) cycle includes exocytosis of vesicles loaded with a neurotransmitter such as glutamate, coordinated recovery of SVs by endocytosis, refilling of vesicles, and subsequent release of the refilled vesicles from the presynaptic bouton. SV exocytosis is tightly linked with endocytosis, and variations in the number of vesicles, and/or defects in the refilling of SVs, will affect the amount of neurotransmitter available for release (Sudhof, 2004). There is increasing interest in the roles synaptic vesicle lipids and lipid metabolizing enzymes play in this recycling. Initial emphasis was placed on the role of polyphosphoinositides in SV cycling as outlined in a number of reviews (Lim and Wenk, 2009; Martin, 2012; Puchkov and Haucke, 2013; Rohrbough and Broadie, 2005). Other lipids are now recognized to also play critical roles. For example, PLD1 (Humeau et al., 2001; Rohrbough and Broadie, 2005) and some DGKs (Miller et al., 1999; Nurrish et al., 1999) play roles in neurotransmission which is consistent with the critical roles for phosphatidic acid (PtdOH) and diacylglycerol (DAG) in the regulation of SV exo/endocytosis (Cremona et al., 1999; Exton, 1994; Huttner and Schmidt, 2000; Lim and Wenk, 2009; Puchkov and Haucke, 2013; Rohrbough and Broadie, 2005). PLD generates phosphatidic acid by catalyzing the hydrolysis of phosphatidylcholine (PtdCho) and in some systems this PtdOH is de-phosphorylated to generate DAG. In contrast, DGK catalyzes the phosphorylation of DAG thereby converting it into PtdOH. While both enzymes are poised to regulate the levels of DAG and PtdOH, therefore, they both lead to the generation of PtdOH and could have opposite effects on DAG levels. This is particularly important for SV cycling as PtdOH and DAG are both needed for evoked exocytosis (Lim and Wenk, 2009; Puchkov and Haucke, 2013; Rohrbough and Broadie, 2005). Two lipids and their involved metabolic enzymes, two sphingolipids have also been implicated in exocytosis: sphingosine (Camoletto et al., 2009; Chan et al., 2012; Chan and Sieburth, 2012; Darios et al., 2009; Kanno et al., 2010; Rohrbough et al., 2004) and sphingosine-1-phosphate (Chan, Hu, 2012; Chan and Sieburth, 2012; Kanno et al., 2010). Finally a number of reports have focused on the somewhat less well studies roles of sphingolipids and cholesterol in SV cycling. In this report, we review the recent understanding of the roles PLDs, DGKs, and DAG lipases, as well as sphingolipids and cholesterol play in synaptic vesicle cycling.
突触小泡（SV）循环包括装载神经递质（如谷氨酸）的小泡的胞吐作用、通过内吞作用对突触小泡的协同回收、小泡的再填充以及随后从突触前终扣释放再填充的小泡。突触小泡胞吐作用与内吞作用紧密相连，小泡数量的变化和/或突触小泡再填充的缺陷会影响可用于释放的神经递质的量（Sudhof，2004）。人们对突触小泡脂质和脂质代谢酶在这种循环中所起的作用越来越感兴趣。如一些综述所述（Lim和Wenk，2009；Martin，2012；Puchkov和Haucke，2013；Rohrbough和Broadie，2005），最初的重点是多磷酸肌醇在突触小泡循环中的作用。现在人们认识到其他脂质也起着关键作用。例如，PLD1（Humeau等人，2001；Rohrbough和Broadie，2005）和一些二酰甘油激酶（DGK）（Miller等人，1999；Nurrish等人，1999）在神经传递中起作用，这与磷脂酸（PtdOH）和二酰甘油（DAG）在调节突触小泡胞吐/内吞作用中的关键作用一致（Cremona等人，1999；Exton，1994；Huttner和Schmidt，2000；Lim和Wenk，2009；Puchkov和Haucke，2013；Rohrbough和Broadie，2005）。PLD通过催化磷脂酰胆碱（PtdCho）的水解产生磷脂酸，在某些系统中，这种PtdOH会去磷酸化生成DAG。相反，DGK催化DAG的磷酸化，从而将其转化为PtdOH。因此，虽然这两种酶都准备调节DAG和PtdOH的水平，但它们都会导致PtdOH的产生，并且可能对DAG水平产生相反的影响。这对突触小泡循环尤为重要，因为诱发的胞吐作用需要PtdOH和DAG（Lim和Wenk，2009；Puchkov和Haucke，2013；Rohrbough和Broadie，2005）。两种脂质及其相关的代谢酶，两种鞘脂也与胞吐作用有关：鞘氨醇（Camoletto等人，2009；Chan等人，2012；Chan和Sieburth，2012；Darios等人，2009；Kanno等人，2010；Rohrbough等人，2004）和鞘氨醇-1-磷酸（Chan，Hu，2012；Chan和Sieburth，2012；Kanno等人，2010）。最后，一些报告关注了鞘脂和胆固醇在突触小泡循环中研究较少的作用。在本报告中，我们综述了对PLD、DGK和DAG脂肪酶以及鞘脂和胆固醇在突触小泡循环中所起作用的最新认识。
