Neuronal Ceroid Lipofuscinoses: Connecting Calcium Signalling through Calmodulin

• Main Authors: Sabateeshan Mathavarajah, Danton H. O’Day, Robert J. Huber
• Format: Article
• Language: English
• Published: MDPI AG 2018-10-01
• Series: Cells
• Subjects: batten disease; neuronal ceroid lipofuscinosis; calmodulin; calmodulin-binding proteins; calmodulin-binding domains; calcium
• Online Access: https://www.mdpi.com/2073-4409/7/11/188

Despite the increased focus on the role of calcium in the neuronal ceroid lipofuscinoses (NCLs, also known as Batten disease), links between calcium signalling and the proteins associated with the disease remain to be identified. A central protein in calcium signalling is calmodulin (CaM), which regulates many of the same cellular processes affected in the NCLs. In this study, we show that 11 of the 13 NCL proteins contain putative CaM-binding domains (CaMBDs). Many of the missense mutations documented from NCL patients overlap with the predicted CaMBDs and are often key residues of those domains. The two NCL proteins lacking such domains, CLN7 and CLN11, share a commonality in undergoing proteolytic processing by cathepsin L, which contains a putative CaMBD. Since CaM appears to have both direct and indirect roles in the NCLs, targeting it may be a valid therapeutic approach for treating the disease.