Dynein-dynactin complex subunits are differentially localized in brain and spinal cord, with selective involvement in pathological features of neurodegenerative disease.
OBJECTIVE
The dynein-dynactin complex, mostly recognized for axonal retrograde transport in neurones, has an ever growing list of essential subcellular functions. Here, the distribution of complex subunits in human central nervous system (CNS) has been assessed using immunohistochemistry in order to test the hypothesis that this may be altered in neurodegenerative disease.


METHODS
Three dynactin and two dynein subunits were immunolocalized in the CNS of human post mortem sections from motor neurone disease, Alzheimer's disease and patients with no neurological disease.


RESULTS
Unexpectedly, coordinated distribution of complex subunits was not evident, even in normal tissues. Complex subunits were differentially localized in brain and spinal cord, and localization of certain subunits, but not others, occurred in pathological structures of motor neurone and Alzheimer's diseases.


CONCLUSIONS
These results suggest that dynein-dynactin complex subunits may have specific subcellular roles, and primary events that disturb the function of individual components may result in disequilibrium of subunit pools, with the possibility that availability for normal cytoplasmic functions becomes impaired, with consequent organelle and axonal transport misfunction.
Ateh
D D
DD
The London Queen Mary's School of Medicine and Dentistry, Queen Mary University of London, London, UK. d.d.ateh@qmul.ac.uk
Hussain
I K
IK
Mustafa
A H
AH
Price
K M
KM
Gulati
R
R
Nickols
C D
CD
Bird
M M
MM
Greensmith
L
L
Hafezparast
M
M
Fisher
E M C
EM
Baker
C S
CS
Martin
J E
JE
D001921:Brain / Q000378:metabolism* / Q000473:pathology; D000072159:Dynactin Complex; D004398:Dyneins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D004398:Dyneins