TY - JOUR
T1 - Distribution of an APP homolog, APLP2, in the mouse olfactory system
T2 - A potential role for APLP2 in axogenesis
AU - Thinakaran, Gopal
AU - Kitt, Cheryl A.
AU - Roskams, A. Jane I.
AU - Slunt, Hilda H.
AU - Masliah, Eliezer
AU - Von Koch, Cornelia
AU - Ginsberg, Stephen D.
AU - Ronnett, Gabriele V.
AU - Reed, Randall R.
AU - Price, Donald L.
AU - Sisodia, Sangram S.
PY - 1995/10
Y1 - 1995/10
N2 - Deposition of β-amyloid (Aβ) in senile plaques is a major pathological characteristic of Alzheimer's disease. Aβ is generated by proteolytic processing of amyloid precursor proteins (APP). APP is a member of a family of related polypeptides that includes amyloid precursor-like proteins APLP1 and APLP2. To examine the distribution of APLP2 in the nervous system, we generated antibodies specific for APLP2 and used these reagents in immunocytochemical and biochemical studies of the rodent nervous system. In this report, we document that in cortex and hippocampus, APLP2 is enriched in postsynaptic compartments. In the olfactory system, however, APLP2 is abundant in olfactory sensory axons, and axon terminals in glomeruli. Confocal microscopy revealed that APLP2 is present in both pre- and postsynaptic compartments in the olfactory bulb. Notably, mRNA encoding chondroitin sulfate glycosaminoglycan (CS GAG)-modified forms of APLP2 are enriched in the olfactory epithelium, relative to alternatively-spliced mRNA, encoding CS GAG-free forms of APLP2. In addition, we demonstrate that CS- modified APLP2 forms accumulate in the olfactory bulb. CS proteoglycans are known to play an important role in regulating cell migration and neuronal outgrowth. Since sensory neurons in the olfactory epithelium are in a state of continual turnover, axons of newly generated cells must establish synaptic connections with neurons in the olfactory bulb in adult life. The presence of APLP2 in olfactory sensory axons and glomeruli is consistent with the view that this protein may play an important role in axonal pathfinding and/or synaptogenesis.
AB - Deposition of β-amyloid (Aβ) in senile plaques is a major pathological characteristic of Alzheimer's disease. Aβ is generated by proteolytic processing of amyloid precursor proteins (APP). APP is a member of a family of related polypeptides that includes amyloid precursor-like proteins APLP1 and APLP2. To examine the distribution of APLP2 in the nervous system, we generated antibodies specific for APLP2 and used these reagents in immunocytochemical and biochemical studies of the rodent nervous system. In this report, we document that in cortex and hippocampus, APLP2 is enriched in postsynaptic compartments. In the olfactory system, however, APLP2 is abundant in olfactory sensory axons, and axon terminals in glomeruli. Confocal microscopy revealed that APLP2 is present in both pre- and postsynaptic compartments in the olfactory bulb. Notably, mRNA encoding chondroitin sulfate glycosaminoglycan (CS GAG)-modified forms of APLP2 are enriched in the olfactory epithelium, relative to alternatively-spliced mRNA, encoding CS GAG-free forms of APLP2. In addition, we demonstrate that CS- modified APLP2 forms accumulate in the olfactory bulb. CS proteoglycans are known to play an important role in regulating cell migration and neuronal outgrowth. Since sensory neurons in the olfactory epithelium are in a state of continual turnover, axons of newly generated cells must establish synaptic connections with neurons in the olfactory bulb in adult life. The presence of APLP2 in olfactory sensory axons and glomeruli is consistent with the view that this protein may play an important role in axonal pathfinding and/or synaptogenesis.
KW - APLP2
KW - APP
KW - alternative splicing
KW - amyloid precursor-like protein 2
KW - chondroitin sulfate glycosaminoglycan
KW - glomeruli
KW - olfactory epithelium
KW - olfactory sensory neurons
UR - http://www.scopus.com/inward/record.url?scp=0028835173&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028835173&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.15-10-06314.1995
DO - 10.1523/jneurosci.15-10-06314.1995
M3 - Article
C2 - 7472397
AN - SCOPUS:0028835173
SN - 0270-6474
VL - 15
SP - 6314
EP - 6326
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 10
ER -