B4GALNT1 dimer transfers GalNAc to gangliosides

Gangliosides are part of the family of glycosphingolipids and are components of the synaptic plasma membrane involved in synaptic plasticity, signal transduction, and endocytosis, processes for CNS development. Complex gangliosides (G) can be mono- (M), di- (D), and tri- (T) sialic acid-containing glycosphingolipids generated by sequential glycosylations in the ER and Golgi. Beta-1,4 N-acetylgalactosaminyltransferase 1 (B4GALNT1), a homodimeric protein (Li et al. 2000) residing on the Golgi membrane, catalyses the transfer of N-acetyl-galactosamine (GalNAc) to gangliosides GM3, GD3, GT3, SM3, and LacCer by a beta-1,4 linkage to produce GM2, GD2, GT2, SM2, and GA2 (Nagata et al., 1992; Yamashiro et al., 1995; reviewed in Sandhoff & Sandhoff, 2018). Defects in B4GALNT1 can cause spastic paraplegia 26 (SPG26, MIM:609195), a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs (Boukhris et al., 2013).

神经节苷脂属糖鞘脂家族，是参与突触可塑性、信号转导和内吞作用等中枢神经系统发育过程的突触浆膜成分。复杂神经节苷脂（G）可通过内质网和高尔基体的连续糖基化生成，包括单唾液酸（M）、双唾液酸（D）和三唾液酸（T）神经节苷脂。β-1,4-唾液酰基转移酶1（B4GALNT1），一种位于高尔基膜上的同源二聚体蛋白（Li et al. 2000），催化N-乙酰半乳糖胺（GalNAc）通过β-1,4键连接到神经节苷脂GM3、GD3、GT3、SM3和LacCer上，从而生成GM2、GD2、GT2、SM2和GA2（Nagata et al., 1992; Yamashiro et al., 1995; Sandhoff & Sandhoff, 2018综述）。B4GALNT1的缺陷可导致痉挛性截瘫26（SPG26，MIM:609195），一种以缓慢、逐渐、进行性下肢无力及痉挛为特征的神经退行性疾病（Boukhris et al., 2013）。