PMID- 22261744
OWN - NLM
STAT- MEDLINE
DCOM- 20120817
LR  - 20211203
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Linking)
VI  - 69
IP  - 12
DP  - 2012 Jun
TI  - Neuronal ceroid lipofuscinosis protein CLN3 interacts with motor proteins and 
      modifies location of late endosomal compartments.
PG  - 2075-89
LID - 10.1007/s00018-011-0913-1 [doi]
AB  - 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.
FAU - Uusi-Rauva, Kristiina
AU  - Uusi-Rauva K
AD  - National Institute for Health and Welfare and FIMM, Institute for Molecular 
      Medicine Finland, Biomedicum Helsinki, Finland.
FAU - Kyttala, Aija
AU  - Kyttala A
FAU - van der Kant, Rik
AU  - van der Kant R
FAU - Vesa, Jouni
AU  - Vesa J
FAU - Tanhuanpaa, Kimmo
AU  - Tanhuanpaa K
FAU - Neefjes, Jacques
AU  - Neefjes J
FAU - Olkkonen, Vesa M
AU  - Olkkonen VM
FAU - Jalanko, Anu
AU  - Jalanko A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120120
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (CLN3 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Molecular Motor Proteins)
RN  - 0 (rab7 GTP-Binding Proteins)
RN  - 0 (rab7 GTP-binding proteins, human)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
SB  - IM
MH  - Endosomes/*metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Lysosomes/metabolism
MH  - Membrane Glycoproteins/genetics/*metabolism
MH  - Molecular Chaperones/genetics/*metabolism
MH  - Molecular Motor Proteins/*metabolism
MH  - Mutation
MH  - Neuronal Ceroid-Lipofuscinoses/*metabolism
MH  - rab GTP-Binding Proteins/metabolism
MH  - rab7 GTP-Binding Proteins
EDAT- 2012/01/21 06:00
MHDA- 2012/08/18 06:00
CRDT- 2012/01/21 06:00
PHST- 2011/06/29 00:00 [received]
PHST- 2011/12/29 00:00 [accepted]
PHST- 2011/12/08 00:00 [revised]
PHST- 2012/01/21 06:00 [entrez]
PHST- 2012/01/21 06:00 [pubmed]
PHST- 2012/08/18 06:00 [medline]
AID - 10.1007/s00018-011-0913-1 [doi]
PST - ppublish
SO  - Cell Mol Life Sci. 2012 Jun;69(12):2075-89. doi: 10.1007/s00018-011-0913-1. Epub 
      2012 Jan 20.