RT Journal Article
SR Electronic
T1 Functional Role of the Interaction between Polysialic Acid and Extracellular Histone H1
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 12400
OP 12413
DO 10.1523/JNEUROSCI.6407-09.2010
VO 30
IS 37
A1 Bibhudatta Mishra
A1 Maren von der Ohe
A1 Christian Schulze
A1 Shan Bian
A1 Tatjana Makhina
A1 Gabriele Loers
A1 Ralf Kleene
A1 Melitta Schachner
YR 2010
UL http://www.jneurosci.org/content/30/37/12400.abstract
AB Polysialic acid (PSA) is a large and highly negatively charged glycan that plays crucial roles in nervous system development and function in the adult. It has been suggested to facilitate cell migration, neurite outgrowth, and synaptic plasticity because its hydration volume could enhance flexibility of cell interactions. Evidence for receptors of PSA has so far been elusive. We now identified histone H1 as binding partner of PSA via a single-chain variable fragment antibody using an anti-idiotypic approach. Histone H1 directly binds to PSA as shown by ELISA. Surface biotinylation of cultured cerebellar neurons indicated an extracellular localization of histone H1. Immunostaining of live cerebellar neurons and Schwann cells confirmed that an extracellular pool of histone H1 colocalizes with PSA at the cell surface. Histone H1 was also detected in detergent-insoluble synaptosomal membrane subfractions and postsynaptic densities. When applied in vitro, histone H1 stimulated neuritogenesis, process formation and proliferation of Schwann cells, and migration of neural precursor cells via a PSA-dependent mechanism, further indicating that histone H1 is active extracellularly. These in vitro observations suggested an important functional role for the interaction between histone H1 and PSA not only for nervous system development but also for regeneration in the adult. Indeed, histone H1 improved functional recovery, axon regrowth, and precision of reinnervation of the motor branch in adult mice with femoral nerve injury. Our findings encourage investigations on the therapeutic potential of histone H1 in humans.