The extracellular-matrix protein matrilin 2 participates in peripheral nerve regeneration
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Date
2009
Authors
Malin, Dmitry
Sonnenberg-Riethmacher, Eva
Guseva, Daria
Wagener, Raimund
Aszódi, Attila
Irintchev, Audrey
Riethmacher, Dieter
Journal Title
Journal ISSN
Volume Title
Publisher
The Company of Biologists
Abstract
Matrilins are adaptor proteins of the extracellular matrix
involved in the formation of both collagen-dependent and
collagen-independent filamentous networks. Although their
molecular structure and binding partners have been
characterized, the functional roles of the four matrilin family
members in vivo are still largely unknown. Here, we show that
matrilin 2, expressed in pre-myelinating Schwann cells during
normal development, profoundly influences the behaviour of
glial cells and neurons in vitro. When offered as a uniform
substrate, matrilin 2 increased neurite outgrowth of dorsal root
ganglia (DRG) neurons and enhanced the migration of both cell
line- and embryonic DRG-derived Schwann cells. Vice versa,
axonal outgrowth and cell migration were decreased in DRG
cultures prepared from matrilin-2-deficient mice compared with
wild-type (wt) cultures. In stripe assays, matrilin 2 alone was
sufficient to guide axonal growth and, interestingly, axons
favoured the combination of matrilin 2 and laminin over
laminin alone. In vivo, matrilin 2 was strongly upregulated in
injured peripheral nerves of adult wild-type mice and failure
of protein upregulation in knockout mice resulted in delayed
regrowth of regenerating axons and delayed time-course of
functional recovery. Strikingly, the functional recovery 2 months
after nerve injury was inferior in matrilin-2-deficient mice
compared with wild-type littermates, although motoneuron
survival, quality of axonal regeneration, estimated by analyses
of axonal diameters and degrees of myelination, and Schwann
cell proliferation were not influenced by the mutation. These
results show that matrilin 2 is a permissive substrate for axonal
growth and cell migration, and that it is required for successful
nerve regeneration
Description
Keywords
Schwann cells, Axonal outgrowth, Extracellular matrix, Coating substrates, Cell migration, Peripheral nerve regeneration
Citation
Dmitry Malin, Eva Sonnenberg-Riethmacher, Daria Guseva, Raimund Wagener, Attila Aszódi, Audrey Irintchev, Dieter Riethmacher; 2009; The extracellular-matrix protein matrilin 2 participates in peripheral nerve regeneration; Journal of Cell Science