Final published version
Research output: Contribution to Journal/Magazine › Review article › peer-review
Research output: Contribution to Journal/Magazine › Review article › peer-review
}
TY - JOUR
T1 - The insulin-like growth factor-II/mannose-6-phosphate receptor
T2 - Structure, distribution and function in the central nervous system
AU - Hawkes, C.
AU - Kar, S.
PY - 2004/3/1
Y1 - 2004/3/1
N2 - The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a multifunctional single transmembrane glycoprotein which, along with the cation-dependent M6P (CD-M6P) receptor, mediates the trafficking of M6P-containing lysosomal enzymes from the trans-Golgi network (TGN) to lysosomes. Cell surface IGF-II/M6P receptors also function in the degradation of the non-glycosylated IGF-II polypeptide hormone, as well as in the capture and activation/degradation of extracellular M6P-bearing ligands. In recent years, the multifaceted role of the receptor has become apparent, as several lines of evidence have indicated that in addition to its role in lysosomal enzyme trafficking, clearance and/or activation of a variety of growth factors and endocytosis-mediated degradation of IGF-II, the IGF-II/M6P receptor may also mediate transmembrane signal transduction in response to IGF-II binding under certain conditions. However, very little is known about the physiological significance of the receptor in the function of the central nervous system (CNS). This review aims to delineate what is currently known about IGF-II/M6P receptor structure, its ligand binding properties and role in lysosomal enzyme transport. It also summarizes the recent data regarding the role of the receptor in the CNS, including its distribution, possible importance for normal and activity-dependent functioning as well as its implications in neurodegenerative disorders such as Alzheimer's disease (AD).
AB - The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a multifunctional single transmembrane glycoprotein which, along with the cation-dependent M6P (CD-M6P) receptor, mediates the trafficking of M6P-containing lysosomal enzymes from the trans-Golgi network (TGN) to lysosomes. Cell surface IGF-II/M6P receptors also function in the degradation of the non-glycosylated IGF-II polypeptide hormone, as well as in the capture and activation/degradation of extracellular M6P-bearing ligands. In recent years, the multifaceted role of the receptor has become apparent, as several lines of evidence have indicated that in addition to its role in lysosomal enzyme trafficking, clearance and/or activation of a variety of growth factors and endocytosis-mediated degradation of IGF-II, the IGF-II/M6P receptor may also mediate transmembrane signal transduction in response to IGF-II binding under certain conditions. However, very little is known about the physiological significance of the receptor in the function of the central nervous system (CNS). This review aims to delineate what is currently known about IGF-II/M6P receptor structure, its ligand binding properties and role in lysosomal enzyme transport. It also summarizes the recent data regarding the role of the receptor in the CNS, including its distribution, possible importance for normal and activity-dependent functioning as well as its implications in neurodegenerative disorders such as Alzheimer's disease (AD).
KW - Development and Regeneration
KW - Endosomal-lysosomal system
KW - Growth factor
KW - Insulin-like growth factor-II receptor
KW - Intracellular trafficking
KW - Mannose 6-phosphate receptor
KW - Neurodegenerative disorders
KW - Neurotrophic factors: receptors and cellular mechanisms
U2 - 10.1016/j.brainresrev.2003.11.002
DO - 10.1016/j.brainresrev.2003.11.002
M3 - Review article
C2 - 15003389
AN - SCOPUS:1442299204
VL - 44
SP - 117
EP - 140
JO - Brain Research Reviews
JF - Brain Research Reviews
SN - 0165-0173
IS - 2-3
ER -