Differential induction and intracellular localization of SCG10 messenger RNA is associated with neuronal differentiation.
The differentiation of neurons involves the establishment of distinct molecular compartments which regulate neuronal shape and function. This requires targeting of specific gene products to growth-associated regions of the neuron. We have investigated the temporal and spatial regulation of SCG10 gene expression during neuronal differentiation. There are two SCG10 messenger RNAs, 1 and 2 kg in length, which encode the same growth-associated protein. These messenger RNAs were found to be differentially regulated during the onset of neurite outgrowth in early rat cerebellum development. In PC12 cells, the two SCG10 messenger RNAs were shown to be differentially induced by nerve growth factor. Regulation of the 2 kb messenger RNA, but not the 1 kb messenger RNA, is dependent on the differentiation of PC12 cells, indicating that post-transcriptional regulation of SCG10 expression during neurite outgrowth. Spatial regulation of the 2 kb SCG10 messenger RNA distribution during brain development was examined by in situ hybridization. The 2 kb messenger RNA was found to be localized to the neuronal pole where outgrowth was occurring, within differentiating neurons in vivo. Intracellular localization of SCG10 messenger RNA was also observed in differentiating primary cultured neurons, with the 2 kb messenger RNA transported into growing neurites during the development of neuronal polarity. In neurons which had developed polarity, the 2 kb SCG10 messenger RNA was consistently found in the cell body and axon. This study demonstrates both temporal and spatial post-transcriptional regulation of SCG10 expression which is associated with neurite outgrowth. The directed transport and positional translation of SCG10 messenger RNA provide a potential mechanism for protein targeting and the creation of molecular compartments during neuronal differentiation.
Hannan
A J
AJ
Developmental Neurobiology Unit, Children's Medical Research Institute, Wentworthville, NSW, Australia.
Henke
R C
RC
Weinberger
R P
RP
Sentry
J W
JW
Jeffrey
P L
PL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured / Q000502:physiology; D002531:Cerebellum / Q000196:embryology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D017403:In Situ Hybridization; D008565:Membrane Proteins; D008868:Microtubule Proteins; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics*; D009420:Nervous System / Q000196:embryology; D009424:Nervous System Physiological Phenomena; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017422:Sequence Analysis, DNA; D017783:Superior Cervical Ganglion / Q000166:cytology* / Q000196:embryology / Q000502:physiology
D002352:Carrier Proteins; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C512848:Stmn2 protein, rat