Regulated shuttling of Slit-Robo-GTPase activating proteins between nucleus and cytoplasm during brain development.
(1) A Little information exists on the distribution of Slit-Robo-GTPase activating proteins (srGAPs), particularly about their intracellular locations, which may provide further clues to their functions. The purpose of this study is to elucidate the expression patterns of the three srGAPs in wild-type rat brains at adult and various developmental stages, and in the cultured cortical neurons. (2) Immunohistochemical method was applied to detect the distribution and localization of the srGAPs in the normal rat brains at adult and various developmental stages, and in the cultured cortical neurons using the rabbit polyclonal antibodies. (3) Immunohistochemical analysis demonstrated that the three srGAPs were mainly expressed in neurons throughout the brain. More importantly, srGAPs translocated during development by a highly regulated shuttling process between the nucleus and the cytoplasm of neurons and their expression patterns were not overlapping. In cultured cortical neurons srGAPs were found in equal amounts in the cytoplasm, nucleus, in neurites, and growth cones. When neurons were maintained in vitro for longer time, the amount of srGAPs in the nucleus strongly increased. (4) These results suggest that srGAPs are not only involved in the regulation of the Slit-Robo signal transduction, but also in neuronal development and that the translocation of srGAPs is important for their functions.
Yao
Qin
Q
Institute of Neurosciences, the Fourth Military Medical University, 17 Chang Le Xi Road, Xi'an, 710032, P.R. China.
Jin
Wei-Lin
WL
Wang
Ying
Y
Ju
Gong
G
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D000918:Antibody Specificity; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
D020690:GTPase-Activating Proteins; C530215:SRGAP3 protein, rat; C530213:srGAP1 protein, rat; C530214:srGAP2 protein, rat
Science. 1986 Aug 15;233(4765):783-6
3738509
Neuron. 2002 Jan 3;33(1):47-61
11779479
Cell. 1999 Mar 19;96(6):795-806
10102268
Science. 1999 Oct 22;286(5440):741-6
10531053
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11754-9
12195014
Cell. 2001 Oct 19;107(2):209-21
11672528
Cell. 1999 Mar 19;96(6):771-84
10102266
Neuron. 1999 Mar;22(3):463-73
10197527
Cell. 1999 Mar 19;96(6):785-94
10102267
Science. 2001 Mar 9;291(5510):1928-38
11239147
J Biol Chem. 2006 Jun 2;281(22):15320-9
16574662
Nat Cell Biol. 2002 Dec;4(12):970-5
12447388
J Biol Chem. 2004 Oct 15;279(42):44197-210
15304504
Genes Dev. 1997 Feb 15;11(4):463-75
9042860
Nature. 1999 Jul 22;400(6742):331-6
10432110
Cell Signal. 2003 Dec;15(12):1071-80
14575862
Brain Res Mol Brain Res. 2004 Apr 7;123(1-2):76-80
15046868
Anal Biochem. 1991 Feb 1;192(2):262-7
1852137
Cell. 1999 Mar 19;96(6):807-18
10102269
J Biol Chem. 2003 Oct 24;278(43):42515-23
12871950
Nat Neurosci. 2002 Nov;5(11):1147-54
12379860
J Biol Chem. 2005 May 6;280(18):18130-7
15749698
J Neurosci. 2000 Jul 1;20(13):4962-74
10864954
J Comp Neurol. 2002 Jan 7;442(2):130-55
11754167
Cancer Lett. 2001 Apr 10;165(1):1-10
11248412