In dystrophic mice, a model of merosin-deficient congenital muscular dystrophy, laminin-2 mutations produce peripheral nerve dysmyelination and render Schwann cells unable to sort bundles of axons. The laminin receptor and the mechanism through which dysmyelination and impaired sorting occur are unknown. We describe mice in which Schwann cell–specific disruption of β1 integrin, a component of laminin receptors, causes a severe neuropathy with impaired radial sorting of axons. β1-null Schwann cells populate nerves, proliferate, and survive normally, but do not extend or maintain normal processes around axons. Interestingly, some Schwann cells surpass this problem to form normal myelin, possibly due to the presence of other laminin receptors such as dystroglycan and α6β4 integrin. These data suggest that β1 integrin links laminin in the basal lamina to the cytoskeleton in order for Schwann cells to ensheath axons, and alteration of this linkage contributes to the peripheral neuropathy of congenital muscular dystrophy.

In dystrophic mice, a model of merosin‐deficient congenital muscular dystrophy, laminin‐2 mutations produce peripheral nerve dysmyelination and render Schwann cells unable to sort bundles of axons. The laminin receptor and the mechanism through which dysmyelination and impaired sorting occur are unknown. We describe mice in which Schwann cell‐specific disruption of beta1 integrin, a component of laminin receptors, causes a severe neuropathy with impaired radial sorting of axons. Beta1‐null Schwann cells populate nerves, proliferate, and survive normally, but do not extend or maintain normal processes around axons. Interestingly, some Schwann cells surpass this problem to form normal myelin, possibly due to the presence of other laminin receptors such as dystroglycan and α6β4 integrin. These data suggest that PI integrin links laminin in the basal lamina to the cytoskeleton in order for Schwann cells to ensheath axons, and alteration of this linkage contributes to the peripheral neuropathy of congenital muscular dystrophy.

The possibility of coexistence of di¡erent subtypes of membrane lipid rafts has been investigated in cerebellar granule cells, by submitting detergent-resistant membrane fractions to immunoprecipitation. Among the proteins and lipids present in detergent-resistant fractions, almost all Prion protein, GAP43 and PKC were present in the immunoprecipitate obtained with anti-GAP43 or anti-Prion protein antibody at 4 ‡C, together with a small fraction of cholesterol and sphingolipids, suggesting that they belong to a distinct subset of membranes. On the contrary, all Fyn and almost all MARCKS remained in the supernatant. Fluorescence microscopy experiments showed that Fyn and Prion protein were mostly not colocalized within a single neuron. Our results suggest that granule cells membranes contains di¡erent subtypes of detergent-resistant fractions, possibly deriving from di¡erent lipid rafts.

IL-1 elicits its cellular effects by binding a heterodimeric receptor consisting of IL-1RI and the accessory protein, IL-1RAcPr. In addition, it binds to IL-1RII, which lacking signaling function has been ascribed a decoy role. The fate of the ligand following interaction with the decoy receptor was examined in human polymorphonuclear cells (PMN), which express predominantly (>90%) IL-1RII. Incubation of PMN with IL-1β results in a rapid decrease in cell surface-associated ligand accompanied by a concomitant increase in internalized IL-1 with 50–60% of IL-1β located intracellularly within 1 h at 37°C. The use of blocking Abs revealed that IL-1 internalization is mediated exclusively by the decoy receptor. The results of inhibitor analysis demonstrate that internalization requires ATP synthesis and involves clathrin-mediated endocytosis. Following removal of the ligand, the receptor was rapidly re-expressed on the cell surface. Cyclohexamide, a protein synthesis inhibitor, had no effect upon the process, suggesting that the re-expressed receptor was recycled. In addition, human keratinocytes stably transfected with IL-1RII (HaCAT 811) also internalized the IL-1RII with 43% cell surface receptor internalized after 90 min. Immunofluorescence microscopy revealed colocalization of the internalized receptor with wheat germ agglutinin-labeled internalized glycoproteins and early endosome Ag-1, a protein associated with the early endosome compartments, indicative of cellular uptake of IL-1RII by endocytosis. In contrast, little or no internalization was observed in other cells of immune origin. These results suggest that the decoy receptor IL-1RII can act as a scavenger of IL-1, representing a novel autoregulatory mechanism of the IL-1 system.

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