Neural regeneration protein is a novel chemoattractive and neuronal survival-promoting factor.
Neurogenesis and neuronal migration are the prerequisites for the development of the central nervous system. We have identified a novel rodent gene encoding for a neural regeneration protein (NRP) with an activity spectrum similar to the chemokine stromal-derived factor (SDF)-1, but with much greater potency. The Nrp gene is encoded as a forward frameshift to the hypothetical alkylated DNA repair protein AlkB. The predicted protein sequence of NRP contains domains with homology to survival-promoting peptide (SPP) and the trefoil protein TFF-1. The Nrp gene is first expressed in neural stem cells and expression continues in glial lineages. Recombinant NRP and NRP-derived peptides possess biological activities including induction of neural migration and proliferation, promotion of neuronal survival, enhancement of neurite outgrowth and promotion of neuronal differentiation from neural stem cells. NRP exerts its effect on neuronal survival by phosphorylation of the ERK1/2 and Akt kinases, whereas NRP stimulation of neural migration depends solely on p44/42 MAP kinase activity. Taken together, the expression profile of Nrp, the existence in its predicted protein structure of domains with similarities to known neuroprotective and migration-inducing factors and the high potency of NRP-derived synthetic peptides acting in femtomolar concentrations suggest it to be a novel gene of relevance in cellular and developmental neurobiology.
Gorba
Thorsten
T
Neuren Pharmaceuticals Ltd., PO Box 9923, Newmarket, Auckland 1031, New Zealand.
Bradoo
Privahini
P
Antonic
Ana
A
Marvin
Keith
K
Liu
Dong-Xu
DX
Lobie
Peter E
PE
Reymann
Klaus G
KG
Gluckman
Peter D
PD
Sieg
Frank
F
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism*; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002630:Chemotactic Factors / Q000378:metabolism*; D018965:Frameshifting, Ribosomal / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013234:Stem Cells / Q000166:cytology
D002630:Chemotactic Factors; D009419:Nerve Tissue Proteins; C514158:Nrp protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D006899:Mixed Function Oxygenases; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3