Regulation of neurite growth in immortalized mouse hypothalamic neurons and rat hippocampal primary cultures by teneurin C-terminal-associated peptide-1

• Published in: Neuroscience 2007-02, Vol.144 (4), p.1241-1254
• Main Authors: Al Chawaf, A, St. Amant, K, Belsham, D, Lovejoy, D.A
• Format: Article
• Language: English
• Subjects: actin; Animals; anxiety; Biological and medical sciences; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Line, Transformed; Cell Proliferation - drug effects; Cells, Cultured; Cytoskeletal Proteins - drug effects; Cytoskeletal Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Growth Cones - drug effects; Growth Cones - metabolism; hippocampus; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Hypothalamus - cytology; Hypothalamus - drug effects; Hypothalamus - metabolism; Mice; Microtubules - drug effects; Microtubules - metabolism; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - pharmacology; Neurites - drug effects; Neurites - metabolism; Neurology; neuropeptide; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; plasticity; Protein Structure, Tertiary - physiology; Rats; Rats, Sprague-Dawley; Tenascin - chemistry; tubulin; Tubulin - drug effects; Tubulin - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2006.09.062

Abstract Teneurins are a highly conserved family of four type II transmembrane proteins that are expressed in the CNS. The protein possesses several functional domains including a unique bioactive 40–41 amino acid sequence at the extracellular terminus. Synthetic versions of this teneurin C-terminal-associated peptide (TCAP) can modulate cyclic AMP accumulation, cell proliferation and teneurin mRNA levels in vitro . Furthermore, i.c.v. injections of TCAP-1 into rat brain induce major changes in acoustic startle response behavior 3 weeks after administration, suggesting that the peptide may act to alter interneuron communication via changes in neurite and axon outgrowth. Synthetic mouse/rat TCAP-1 was used to treat cultured immortalized mouse hypothalamic cells, to determine if TCAP-1 could directly regulate neurite and axon growth. TCAP-1-treated cells showed a significant increase in the length of neurites accompanied by a marked increase in β-tubulin transcription and translation as determined by real-time PCR and Western blot analysis, respectively. Changes in α-actinin-4 transcription and β-actin protein expression were also noted. Immunofluorescence confocal microscopy using β-tubulin antiserum showed enhanced resolution of β-tubulin cytoskeletal elements throughout the cell. In order to determine if the effects of TCAP-1 could be reproduced in primary neuronal cultures, primary cultures of E18 rat hippocampal cells were treated with 100 nM TCAP-1. The TCAP-1-treated hippocampal cultures showed a significant increase in both the number of cells, dendritic branching and the presence of large and fasciculated β-tubulin immunoreactive axons. These data suggest that TCAP acts, in part, as a functional region of the teneurins to regulate neurite and axonal growth of neurons.