PMID- 10036229
OWN - NLM
STAT- MEDLINE
DCOM- 19990504
LR  - 20161124
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 112 ( Pt 6)
DP  - 1999 Mar
TI  - Opposing motor activities of dynein and kinesin determine retention and transport
      of MHC class II-containing compartments.
PG  - 785-95
AB  - MHC class II molecules exert their function at the cell surface by presenting to 
      T cells antigenic fragments that are generated in the endosomal pathway. The
      class II molecules are targetted to early lysosomal structures, termed MIIC,
      where they interact with antigenic fragments and are subsequently transported to 
      the cell surface. We previously visualised vesicular transport of MHC class
      II-containing early lysosomes from the microtubule organising centre (MTOC)
      region towards the cell surface in living cells. Here we show that the MIIC move 
      bidirectionally in a 'stop-and-go' fashion. Overexpression of a motor
      head-deleted kinesin inhibited MIIC motility, showing that kinesin is the motor
      that drives its plus end transport towards the cell periphery. Cytoplasmic dynein
      mediates the return of vesicles to the MTOC area and effectively retains the
      vesicles at this location, as assessed by inactivation of dynein by
      overexpression of dynamitin. Our data suggest a retention mechanism that
      determines the perinuclear accumulation of MIIC, which is the result of dynein
      activity being superior over kinesin activity. The bidirectional nature of MIIC
      movement is the result of both kinesin and dynein acting reciprocally on the MIIC
      during its transport. The motors may be the ultimate targets of regulatory
      kinases since the protein kinase inhibitor staurosporine induces a massive
      release of lysosomal vesicles from the MTOC region that is morphologically
      similar to that observed after inactivation of the dynein motor.
FAU - Wubbolts, R
AU  - Wubbolts R
AD  - Netherlands Cancer Institute, Department of Tumor Biology, Plesmanlaan 121, The
      Netherlands.
FAU - Fernandez-Borja, M
AU  - Fernandez-Borja M
FAU - Jordens, I
AU  - Jordens I
FAU - Reits, E
AU  - Reits E
FAU - Dusseljee, S
AU  - Dusseljee S
FAU - Echeverri, C
AU  - Echeverri C
FAU - Vallee, R B
AU  - Vallee RB
FAU - Neefjes, J
AU  - Neefjes J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Antibodies)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (HLA-D Antigens)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 3.6.4.2 (Dyneins)
RN  - EC 3.6.4.4 (Kinesin)
SB  - IM
MH  - Antibodies
MH  - Antibodies, Monoclonal
MH  - Dyneins/*physiology
MH  - HLA-D Antigens/genetics/*metabolism
MH  - Humans
MH  - Kinesin/*physiology
MH  - Lysosomes/*physiology
MH  - Microscopy, Confocal
MH  - Microtubules/*physiology
MH  - Recombinant Fusion Proteins/metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1999/02/26 00:00
MHDA- 1999/02/26 00:01
CRDT- 1999/02/26 00:00
PHST- 1999/02/26 00:00 [pubmed]
PHST- 1999/02/26 00:01 [medline]
PHST- 1999/02/26 00:00 [entrez]
PST - ppublish
SO  - J Cell Sci. 1999 Mar;112 ( Pt 6):785-95.