Differential expression and function of apoptosis-associated tyrosine kinase (AATYK) in the developing mouse brain.
Apoptosis-associated tyrosine kinase (AATYK) is a non-receptor type tyrosine kinase that is predominantly expressed in adult mouse brain. Although it is also expressed in developing brains, its expression pattern and physiological functions are unclear. In the present study, we analyzed expression profiles of AATYK in developing mouse brains and its functional role and subcellular localization in cultured cerebellar granule cells. Expression of AATYK mRNA and protein increased during postnatal brain development. Immunohistochemical analysis indicated that the protein was differentially expressed in postmitotic neurons within various brain areas including the olfactory bulb, cerebral cortex, hippocampus, thalamus, colliculus, cerebellum, and brain stem. Developmental increases in its expression were also observed in cultured cerebellar granule cells. AATYK protein was largely fractionated into the microsomal fraction and was immunocytochemically distributed in an ER-like meshwork of the granule cell soma, suggesting a possible association with the ER membrane. AATYK protein was also present in neurites. In immature granule cells, overexpression of wild-type AATYK promoted neurite outgrowth, whereas that of tyrosine kinase-defective mutant significantly inhibited it. These results suggest that, in addition to its role in cell death in mature neurons, AATYK has a unique role in promoting neurite extension through its tyrosine kinase activity in developing neurons.
Tomomura
Mineko
M
Laboratory for Cellular Information Processing, Brain Science Institute (BSI), RIKEN, Wako, Japan. mtomomura@brain.riken.go.jp
Hasegawa
Yuki
Y
Hashikawa
Tsutomu
T
Tomomura
Akito
A
Yuzaki
Michisuke
M
Furuichi
Teiichi
T
Yano
Ryoji
R
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001921:Brain / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D002451:Cell Compartmentation / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation / Q000235:genetics; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger; C485554:Aatk protein, mouse; D011505:Protein-Tyrosine Kinases