Data_Sheet_1_Transmembrane Batten Disease Proteins Interact With a Shared Network of Vesicle Sorting Proteins, Impacting Their Synaptic Enrichment.PDF

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病在溶酶体储存病中独具特色，其早期且显著的神经系统表现尤为突出，然而关于疾病相关蛋白在神经元中可能具有的特异性作用，知之甚少。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，并且其缺失会导致关键伙伴（即SNARE蛋白和连接蛋白）的突触耗竭以及体内突触SNARE复合物的改变，从而证明了这一疾病的新型共有病因学特征。