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Inhibition of N‐glycan processing alters axonal transport of synaptic glycoproteins in vivo

McFarlane, Ian; Breen, Kieran C.; Giamberardino, Luigi Di; Moya, Kenneth L.


Synaptic glycoproteins are synthesized and glycosylated in the neuronal cell body, and conveyed to terminals by fast axonal transport. We used the α‐mannosidase inhibitor, 2‐deoxyman‐nojirimycin (dMan), to investigate the effects of disrupting N‐glycan processing on the axonal trafficking of proteins in vivo. dMan significantly reduced rapid axonal transport in retinal ganglion cells to about 34% of control values 4 h after metabolic labeling; at 8 h post‐labeling the inhibition was reversed. 2‐D gel analysis showed that dMan completely inhibited the arrival of radiolabeled L1 and NCAM at axon terminals, and resulted in the appearance of two novel proteins of 230 kDa and 155 kDa. Our results show that disruption of the N‐glycosylation pathway has an immediate inhibitory effect on total axonal transport and longer lasting effects on the trafficking of specific glycoproteins to axon terminals in vivo.

1 Department of Pharmacology and Neuroscience, University of Dundee, Ninewells Hospital Medical School, Dundee DDI 9SY, Scotland, UK

2 INSERM U334, Service Hospitalier Freédeéric Joliot, 4 Place du Geéneéral Leclerc, 91401 Orsay, Cedex, France

3 CEA‐CNRS URA 2210, Service Hospitalier Freédeéric Joliot, 4 Place du Geéneéral Leclerc, 91401 Orsay, Cedex, France

4 Present address: Department of Clinical Biochemistry, Box 232, Addenbrooke's Hosptial, Hills Road, Cambridge CB2 2QQ, UK

5 Corresponding Author: Kenneth L. Moya

Acknowledgements: We thank C. Lagenaur, for anti‐L1, S. S. Sisodia and G. Thinakaran for the anti‐AβPP and APLP2 antibodies. This work was supported by Ciba‐Giegy (ACE Award), the Scottish Hospital Endowments Research Trust, INSERM, CNRS and CEA.

© 2000 Wolters Kluwer Health | Lippincott Williams & Wilkins