Localization and processing of CLN3, the protein associated to batten disease: Where is it and what does it do?

Abstract

Although the CLN3 gene for Batten disease, the most common inherited neurovisceral storage disease of childhood, was identified in 1995, the function of the corresponding protein still remains elusive. A key to understanding the pathology of this devastating disease will be to elucidate the function of CLN3 at the molecular level. CLN3 has proven difficult to study, as it is predicted to be a membrane protein, and is of apparently low abundance in cells. Different groups have reported differing subcellular localization of CLN3. The purpose of this review is to critically examine the various cell biological approaches undertaken to localize CLN3 and to piece together a potential function for CLN3 in neuronal cells. The most likely conclusion of this is that CLN3 is a lysosomal/endosomal protein that is trafficked through the endoplasmic reticulum (ER) and Golgi. Furthermore, studies are required to confirm whether CLN3 has a potential role in the recycling of synaptic vesicles through the endosome/lysosome.

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) and the Eye

“…16, 27, 34, 39, 55, 66, 67, 71–74 Nevertheless, it appears likely that CLN3 is a lysosomal/endosomal protein that is trafficked through the endoplasmic reticulum and Golgi apparatus. 69, 75 The only study addressing CLN3 localization in the retina utilized a peptide antibody raised to a portion of CLN3 in mice. The resulting immunohistochemistry pointed to a mitochondrial localization, predominantly in Müller cells and in neurons in the inner nuclear layer, with only moderate amounts in photoreceptor inner segment mitochondria.…”

Interaction with Btn2p Is Required for Localization of Rsg1p: Btn2p-Mediated Changes in Arginine Uptake in Saccharomyces cerevisiae

“…1,2002 EFFECT OF Btn2p ON ARGININE UPTAKE IN S. CEREVISIAE 611 study of the effects of loss of the human CLN3 gene and colocalization of the human Cln3 protein to synaptic vesicles in neuronal cells (7,9). A disturbance in the lysosomal content or the levels of certain amino acids, particularly in neurons, may result in a perturbation in the trafficking of proteins implicated in neurotransmission (19) or may directly interfere with metabolism of amino acids involved in neurotransmission, contributing to the causation of Batten disease.…”