Neuronal ceroid lipofuscinosis protein CLN3 interacts with motor proteins and modifies location of late endosomal compartments

Cell Mol Life Sci. 2012 Jun;69(12):2075-89. doi: 10.1007/s00018-011-0913-1. Epub 2012 Jan 20.


CLN3 is an endosomal/lysosomal transmembrane protein mutated in classical juvenile onset neuronal ceroid lipofuscinosis, a fatal inherited neurodegenerative lysosomal storage disorder. The function of CLN3 in endosomal/lysosomal events has remained elusive due to poor understanding of its interactions in these compartments. It has previously been shown that the localisation of late endosomal/lysosomal compartments is disturbed in cells expressing the most common disease-associated CLN3 mutant, CLN3∆ex7-8 (c.462-677del). We report here that a protracted disease causing mutant, CLN3E295K, affects the properties of late endocytic compartments, since over-expression of the CLN3E295K mutant protein in HeLa cells induced relocalisation of Rab7 and a perinuclear clustering of late endosomes/lysosomes. In addition to the previously reported disturbances in the endocytic pathway, we now show that the anterograde transport of late endosomal/lysosomal compartments is affected in CLN3 deficiency. CLN3 interacted with motor components driving both plus and minus end microtubular trafficking: tubulin, dynactin, dynein and kinesin-2. Most importantly, CLN3 was found to interact directly with active, guanosine-5'-triphosphate (GTP)-bound Rab7 and with the Rab7-interacting lysosomal protein (RILP) that anchors the dynein motor. The data presented in this study provide novel insights into the role of CLN3 in late endosomal/lysosomal membrane transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endosomes / metabolism*
  • HeLa Cells
  • Humans
  • Lysosomes / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Molecular Motor Proteins / metabolism*
  • Mutation
  • Neuronal Ceroid-Lipofuscinoses / metabolism*
  • rab GTP-Binding Proteins / metabolism


  • CLN3 protein, human
  • Membrane Glycoproteins
  • Molecular Chaperones
  • Molecular Motor Proteins
  • rab7 protein
  • rab GTP-Binding Proteins