Identification and transport of full-length amyloid precursor proteins in rat peripheral nervous system.
Amyloid deposits are a characteristic feature of the senile plaques identified in the brains of aged primates, individuals with Down's syndrome, and cases of Alzheimer's disease. The beta-amyloid protein (A beta), the principal component of amyloid, is a 4 kDa peptide derived from larger amyloid precursor protein(s) (APP). Four mRNAs, generated by alternative splicing of pre-mRNA derived from a single gene, encode A beta-containing membrane glycoproteins termed APP-695, -714, -751, and -770; the latter two isoforms contain a domain homologous to Kunitz protease inhibitors (KPI). The present study uses in vitro and in vivo strategies to examine the expression of APP in neurons of the dorsal root ganglia and the nature of APP transported in sciatic nerves of rats. Using quantitative in situ hybridization and semiquantitative PCR analysis, we document that mRNAs encoding APP-695 are expressed preferentially over transcripts that encode KPI-containing isoforms in rat sensory ganglia. Furthermore, we provide compelling evidence that APP-695 is the predominant isoform synthesized in sensory neurons of the rat PNS and that full-length APP-695 and, to a lesser extent, APP-751/770 are rapidly transported anterogradely in axons.
Sisodia
S S
SS
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196.
Koo
E H
EH
Hoffman
P N
PN
Perry
G
G
Price
D L
DL
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D005727:Ganglia, Spinal / Q000378:metabolism*; D015870:Gene Expression; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009410:Nerve Degeneration; D009475:Neurons, Afferent / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D012584:Sciatic Nerve / Q000378:metabolism*; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger