P-type lectins

Up-Regulation of Cation-Independent Mannose 6-Phosphate Receptor and Endosomal-Lysosomal Markers in Surviving Neurons after 192-IgG-Saporin Administrations into the Adult Rat Brain

“…This was accompanied by a selective time-dependent increase in EL markers, ie, cathepsin D, Rab5, and LAMP2 in the affected regions of treated rats. Because CI-MPR plays a critical role in delivering lysosomal enzymes to the EL system, which is involved in the turnover of damaged proteins and structural reorganization in response to changing conditions, 5,6,9,11,13 it is likely that the observed increases in CI-MPR levels and that of other EL components in surviving neurons represent an adaptive mechanisms to restore metabolic and structural abnormalities that follow 192-IgG-saporin-induced loss of the forebrain cholinergic neurons.…”

“…5,9 At the cellular level, cathepsin D immunoreactivity was evident in a wide spectrum of neurons, but not in glial cells, in both the basal forebrain and frontal cortex of saline-treated animals. Double-immunolabeling experiments also demonstrated the co-localization of cathepsin D with CI-MPRand ChAT-positive neurons within the basal forebrain ( Figure 5, I-L) and frontal cortex of the control rats.…”

“…[1][2][3][4][5][6] The receptor is widely expressed in various tissues including the brain and recognizes, via distinct sites, two different classes of ligands: M6P-containing molecules such as lysosomal enzymes, and IGF-II, a mitogenic polypeptide with structural homology to IGF-I and insulin. 2,7,8 A subpopulation of the CI-MPR is located at the plasma membrane, where it regulates internalization of IGF-II and various exogenous M6P-containing ligands for subsequent clearance or activation.…”

“…2,7,8 A subpopulation of the CI-MPR is located at the plasma membrane, where it regulates internalization of IGF-II and various exogenous M6P-containing ligands for subsequent clearance or activation. However, the majority of the receptors are expressed in the trans-Golgi network/endosomal compartments and are involved in the intracellular trafficking of a battery of lysosomal enzymes including cathepsins B and D. 1,2,5,9,10 Given the evidence that defects in the synthesis/targeting of lysosomal enzymes or dysfunction of the endosomal-lysosomal (EL) system are associated with a variety of neurodegenerative disorders, often with progressive cognitive decline, [11][12][13][14] it is possible that the CI-MPR may have a role in regulating neuronal viability. In fact, a number of studies have shown that loss of CI-MPR function can induce cell proliferation in a variety of cancers.…”

Binding of Urokinase-type Plasminogen Activator Receptor (uPAR) to the Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor

“…The extracytoplasmic region consists of 15 homologous repeats ϳ147 residues in length (1). Separate regions in the receptor's extracytoplasmic domain have been shown to interact with two classes of ligands, insulin-like growth factor II (IGF-II) and proteins that contain a Man-6-P marker as a result of posttranslational modification (2,3).…”