Novel interactions of CLN5 support molecular networking between Neuronal Ceroid Lipofuscinosis proteins

• Published in: BMC Cell Biology Vol. 10; no. 1; p. 83
• Main Authors: Lyly, Annina, von Schantz, Carina, Heine, Claudia, Schmiedt, Mia-Lisa, Sipilä, Tessa, Jalanko, Anu, Kyttälä, Aija
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.11.2009; BioMed Central; BMC
• Subjects: Animals; Cell interaction; Cell Line; Chlorocebus aethiops; Cloning; Endoplasmic Reticulum - metabolism; Golgi Apparatus - metabolism; Laboratory animals; Lipids; Lysosomal Membrane Proteins; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuronal Ceroid-Lipofuscinoses - metabolism; Physiological aspects; Polyclonal antibodies; Protein Binding; Protein Transport; Proteins; Proton-Translocating ATPases - metabolism; Research article; Tripeptidyl-Peptidase 1; United States
• ISSN: 1471-2121; 1741-7007; 1471-2121
• DOI: 10.1186/1471-2121-10-83

Neuronal ceroid lipofuscinoses (NCLs) comprise at least eight genetically characterized neurodegenerative disorders of childhood. Despite of genetic heterogeneity, the high similarity of clinical symptoms and pathology of different NCL disorders suggest cooperation between different NCL proteins and common mechanisms of pathogenesis. Here, we have studied molecular interactions between NCL proteins, concentrating specifically on the interactions of CLN5, the protein underlying the Finnish variant late infantile form of NCL (vLINCLFin). We found that CLN5 interacts with several other NCL proteins namely, CLN1/PPT1, CLN2/TPP1, CLN3, CLN6 and CLN8. Furthermore, analysis of the intracellular targeting of CLN5 together with the interacting NCL proteins revealed that over-expression of PPT1 can facilitate the lysosomal transport of mutated CLN5FinMajor, normally residing in the ER and in the Golgi complex. The significance of the novel interaction between CLN5 and PPT1 was further supported by the finding that CLN5 was also able to bind the F1-ATPase, earlier shown to interact with PPT1. We have described novel interactions between CLN5 and several NCL proteins, suggesting a modifying role for these proteins in the pathogenesis of individual NCL disorders. Among these novel interactions, binding of CLN5 to CLN1/PPT1 is suggested to be the most significant one, since over-expression of PPT1 was shown to influence on the intracellular trafficking of mutated CLN5, and they were shown to share a binding partner outside the NCL protein spectrum.