A potential interactome map of CLN8 protein involved in the late-infantile form of neuronal ceroid lipofuscinosis.

Neuronal ceroid lipofucinoses (NCLs) are a group of inherited neurodegenerative lysosomal storage diseases mainly occurring in childhood. NCL disorders result from mutations in different genes (CLN1-10) and are characterized by progressive neuronal death, leading to manifestation of epilepsy, loss of vision, progressive mental and physical decline and a reduced lifespan. Pathogenic mechanisms are still unknown and no cure is available. We have recently showed that in the CLN8 mnd mouse, the oxidative stress, lipid peroxidation, inflammation and ER stress take place in certain neuronal types and are likely associated to autophago-lysosomal system and mitochondrial dysfunction in the progression of the disease. CLN8 gene code for a transmembrane protein located in the endoplasmic reticulum (ER) and partially in the ER-Golgi intermediate compartment whose function is still unknown. Based to the high homology with the TCL-domain (TRAM- LAG1- CLN8), the CLN8 protein is presumed to be involved in the lipid synthesis and transport. Here, we screen for possible interactors of CLN8 using the Split-Ubiquitin Membrane Yeast Two-Hybrid system. We will show a list of novels binding partners of CLN8p in a human brain cDNA library and preliminary results on the functional role of CLN8p in the sphingolipid synthesis.