TY - JOUR
T1 - Neuraminidase-dependent degradation of polysialic acid is required for the lamination of newly generated neurons
AU - Sajo, Mari
AU - Sugiyama, Hiroki
AU - Yamamoto, Hideaki
AU - Tanii, Takashi
AU - Matsuki, Norio
AU - Ikegaya, Yuji
AU - Koyama, Ryuta
N1 - Funding Information:
This work was in part supported by JSPS KAKENHI Grant Numbers 21790059, 26460094, and 26117504 and in part by the grants for iPS Nonclinical 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. The authors would like to thank Dr Tatsunori Seki for generously providing the anti-PSA antibody. 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.
Publisher Copyright:
© 2016 Sajo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/1/5
Y1 - 2016/1/5
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0146398
DO - 10.1371/journal.pone.0146398
M3 - Article
C2 - 26731280
AN - SCOPUS:84953911433
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 1
M1 - e0146398
ER -