Data_Sheet_2_Transmembrane Batten Disease Proteins Interact With a Shared Network of Vesicle Sorting Proteins, Impacting Their Synaptic Enrichment.docx

Batten disease is unique among lysosomal storage disorders for the early and profound manifestation in the central nervous system, but little is known regarding potential neuron-specific roles for the disease-associated proteins. We demonstrate substantial overlap in the protein interactomes of three transmembrane Batten proteins (CLN3, CLN6, and CLN8), and that their absence leads to synaptic depletion of key partners (i.e., SNAREs and tethers) and altered synaptic SNARE complexing in vivo, demonstrating a novel shared etiology.

Batten病在溶酶体储存障碍中独树一帜，其特征在于中枢神经系统的早期且严重表现，然而关于疾病相关蛋白在神经元特异性角色方面的研究却鲜有进展。本研究揭示了三种跨膜Batten蛋白（CLN3、CLN6和CLN8）的蛋白质互作网络存在显著的重叠，并且它们的缺失会导致关键伙伴（即SNAREs和tethers）的突触耗竭，并在体内改变了SNARE复合物的突触组装，从而证实了一种新型的共有病因。