Cellular prion protein/laminin receptor: distribution in adult central nervous system and characterization of an isoform associated with a subtype of cortical neurons.
The 67-kDa LR protein was originally discovered as a non-integrin laminin receptor. Several more recent in vitro studies demonstrated the function of 67-kDa LR and its related 'precursor' form 37-kDa LRP as receptors of cellular prion protein and their implication in abnormal prion protein propagation in vitro. In addition, expression of both proteins was shown to increase considerably in the brain of scrapie-infected mice and hamsters. While LRP/LR are thus likely to play important roles in neuronal cell adhesion, survival and homeostasis and during pathological disorders, little is known so far about their fine cellular distribution in adult central nervous system. Using immunocytochemistry and western blotting, we show here that the 67-kDa LR is the major receptor form in adult rat brain and spinal cord, expressed within the cytoplasm and at the plasma membrane of most neurons and in a subset of glial cells. The overall distribution of LR correlates well with that reported for laminin-1 but also with brain regions classically associated with prion-related neurodegeneration. In contrast to LR, the 37-kDa LRP form is much less abundant in adult than in postnatal central nervous system. Characterization of a novel antibody allowed us to study the distribution across tissues of cell membrane-associated LRP. Interestingly, this form is almost exclusively found on a subclass of parvalbumin-immunoreactive cortical interneurons known to degenerate during the early stages of Creutzfeldt-Jakob disease. Our demonstration of local differences in the expression of particular LRP/LR isoforms may be a first step towards unraveling their specific molecular interactions.
Baloui
Hasna
H
UMR CNRS 7101, Université Pierre et Marie Curie (Paris 6), 7 quai St Bernard, 75005 Paris, France.
von Boxberg
Ysander
Y
Vinh
Joëlle
J
Weiss
Stefan
S
Rossier
Jean
J
Nothias
Fatiha
F
Stettler
Olivier
O
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000918:Antibody Specificity / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D064026:Calbindins; D002462:Cell Membrane / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology*; D002645:Chickens; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D037121:Plant Lectins / Q000378:metabolism; D011247:Pregnancy; D011328:Prions / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017474:Receptors, Laminin / Q000378:metabolism*; D034781:Receptors, N-Acetylglucosamine; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D000911:Antibodies, Monoclonal; D064026:Calbindins; D005904:Glial Fibrillary Acidic Protein; D010320:Parvalbumins; D037121:Plant Lectins; D011328:Prions; D011498:Protein Precursors; D017474:Receptors, Laminin; D034781:Receptors, N-Acetylglucosamine; D064030:S100 Calcium Binding Protein G; C040129:wisteria lectin