title: Regulated shuttling of Slit-Robo-GTPase activating proteins between nucleus and cytoplasm during brain development.
abstract: (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.
authors: Institute of Neurosciences, the Fourth Military Medical University, 17 Chang Le Xi Road, Xi'an, 710032, P.R. China.
authors: Qin
authors: Q
authors: Yao
authors: Wei-Lin
authors: WL
authors: Jin
authors: Ying
authors: Y
authors: Wang
authors: Gong
authors: G
authors: Ju
mesh_terms: 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
chemical_list: D020690:GTPase-Activating Proteins; C530215:SRGAP3 protein, rat; C530213:srGAP1 protein, rat; C530214:srGAP2 protein, rat
references: Science. 1986 Aug 15;233(4765):783-6
references: 3738509
references: Neuron. 2002 Jan 3;33(1):47-61
references: 11779479
references: Cell. 1999 Mar 19;96(6):795-806
references: 10102268
references: Science. 1999 Oct 22;286(5440):741-6
references: 10531053
references: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11754-9
references: 12195014
references: Cell. 2001 Oct 19;107(2):209-21
references: 11672528
references: Cell. 1999 Mar 19;96(6):771-84
references: 10102266
references: Neuron. 1999 Mar;22(3):463-73
references: 10197527
references: Cell. 1999 Mar 19;96(6):785-94
references: 10102267
references: Science. 2001 Mar 9;291(5510):1928-38
references: 11239147
references: J Biol Chem. 2006 Jun 2;281(22):15320-9
references: 16574662
references: Nat Cell Biol. 2002 Dec;4(12):970-5
references: 12447388
references: J Biol Chem. 2004 Oct 15;279(42):44197-210
references: 15304504
references: Genes Dev. 1997 Feb 15;11(4):463-75
references: 9042860
references: Nature. 1999 Jul 22;400(6742):331-6
references: 10432110
references: Cell Signal. 2003 Dec;15(12):1071-80
references: 14575862
references: Brain Res Mol Brain Res. 2004 Apr 7;123(1-2):76-80
references: 15046868
references: Anal Biochem. 1991 Feb 1;192(2):262-7
references: 1852137
references: Cell. 1999 Mar 19;96(6):807-18
references: 10102269
references: J Biol Chem. 2003 Oct 24;278(43):42515-23
references: 12871950
references: Nat Neurosci. 2002 Nov;5(11):1147-54
references: 12379860
references: J Biol Chem. 2005 May 6;280(18):18130-7
references: 15749698
references: J Neurosci. 2000 Jul 1;20(13):4962-74
references: 10864954
references: J Comp Neurol. 2002 Jan 7;442(2):130-55
references: 11754167
references: Cancer Lett. 2001 Apr 10;165(1):1-10
references: 11248412