Neuraminidase-Dependent Degradation of Polysialic Acid Is Required for the Lamination of Newly Generated Neurons

PLoS One. 2016 Jan 5;11(1):e0146398. doi: 10.1371/journal.pone.0146398. eCollection 2016.

Abstract

Hippocampal granule cells (GCs) are generated throughout the lifetime and are properly incorporated into the innermost region of the granule cell layer (GCL). Hypotheses for the well-regulated lamination of newly generated GCs suggest that polysialic acid (PSA) is present on the GC surface to modulate GC-to-GC interactions, regulating the process of GC migration; however, direct evidence of this involvement is lacking. We show that PSA facilitates the migration of newly generated GCs and that the activity of N-acetyl-α-neuraminidase 1 (NEU1, sialidase 1) cleaves PSA from immature GCs, terminating their migration in the innermost GCL. Developing a migration assay of immature GCs in vitro, we found that the pharmacological depletion of PSA prevents the migration of GCs, whereas the inhibition of PSA degradation with a neuraminidase inhibitor accelerates this migration. We found that NEU1 is highly expressed in immature GCs. The knockdown of NEU1 in newly generated GCs in vivo increased PSA presence on these cells, and attenuated the proper termination of GC migration in the innermost GCL. In conclusion, this study identifies a novel mechanism that underlies the proper lamination of newly generated GCs through the modulation of PSA presence by neuronal NEU1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / physiology
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Neuraminidase / metabolism*
  • Neurogenesis
  • Neurons / cytology
  • Neurons / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Sialic Acids / metabolism*

Substances

  • Sialic Acids
  • polysialic acid
  • Neuraminidase

Grant support

This work was in part supported by JSPS KAKENHI Grant Numbers 21790059, 26460094, and 26117504 and in part by the grants for iPS Non-clinical Experiments for Nervous System (iNCENS) project in AMED. MS was supported by a Grant-in-Aid for JSPS Fellows (No. 10592) from the Japan Society for the Promotion of Science. The authors declare no conflict of interests. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.