601 research outputs found
N-Glycosylation of Γ4 Integrin Controls the Adhesion and Motility of Keratinocytes
Ξ±6Γ4 integrin is an essential component of hemidesmosomes and modulates cell migration in wound healing and cancer invasion. To elucidate the role of N-glycosylation on Γ4 integrin, we investigated keratinocyte adhesion and migration through the re-expression of wild-type or N-glycosylation-defective Γ4 integrin (ΞNΓ4) in Γ4 integrin null keratinocytes. N-glycosylation of Γ4 integrin was not essential for the heterodimer formation of Γ4 integrin with Ξ±6 integrin and its expression on a cell surface, but N-glycosylation was required for integrin-mediated cell adhesion and migration. Concomitantly with the reduction of Γ4 integrin in the membrane microdomain, the intracellular signals of Akt and ERK activation were decreased in cells expressing ΞNΓ4 integrin. Forced cross-linking of Γ4 integrin rescued the decreased ERK activation in ΞNΓ4 integrin-expressing cells to a similar extent in wild-type Γ4 integrin-expressing cells. Surprisingly, compared with cells expressing wild-type Γ4 integrin, an alternation in N-glycan structures expressed on epidermal growth factor receptor (EGFR), and the induction of a stronger association between EGFR and Γ4 integrin were observed in ΞNΓ4 integrin-expressing cells. These results clearly demonstrated that N-glycosylation on Γ4 integrin plays an essential role in keratinocyte cellular function by allowing the appropriate complex formation on cell surfaces
Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy
Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA
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