title: Fine-tuning of neuronal architecture requires two profilin isoforms.
abstract: Two profilin isoforms (PFN1 and PFN2a) are expressed in the mammalian brain. Although profilins are essential for regulating actin dynamics in general, the specific role of these isoforms in neurons has remained elusive. We show that knockdown of the neuron-specific PFN2a results in a significant reduction in dendrite complexity and spine numbers of hippocampal neurons. Overexpression of PFN1 in PFN2a-deficient neurons prevents the loss of spines but does not restore dendritic complexity. Furthermore, we show that profilins are involved in differentially regulating actin dynamics downstream of the pan-neurotrophin receptor (p75(NTR)), a receptor engaged in modulating neuronal morphology. Overexpression of PFN2a restores the morphological changes in dendrites caused by p75(NTR) overexpression, whereas PFN1 restores the normal spine density. Our data assign specific functions to the two PFN isoforms, possibly attributable to different affinities for potent effectors also involved in actin dynamics, and suggest that they are important for the signal-dependent fine-tuning of neuronal architecture.
authors.affiliation: Zoological Institute, University of Braunschweig, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Michaelsen
authors.forename: Kai
authors.initials: K
authors.lastname: Murk
authors.forename: Marta
authors.initials: M
authors.lastname: Zagrebelsky
authors.forename: Anita
authors.initials: A
authors.lastname: Dreznjak
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Jockusch
authors.forename: Martin
authors.initials: M
authors.lastname: Rothkegel
authors.forename: Martin
authors.initials: M
authors.lastname: Korte
mesh_terms: D000818:Animals; D001483:Base Sequence; D055785:Gene Knockdown Techniques; D007150:Immunohistochemistry; D051379:Mice; D009474:Neurons / Q000166:cytology*; D051304:Profilins / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D051304:Profilins; D020033:Protein Isoforms
references.citation: EMBO J. 1998 Feb 16;17(4):967-76
references.pmid: 9463375
references.citation: Eur J Neurosci. 2005 Jan;21(1):15-25
references.pmid: 15654839
references.citation: J Neurosci. 2007 Jan 31;27(5):1097-105
references.pmid: 17267564
references.citation: J Cell Biol. 2003 Sep 29;162(7):1267-79
references.pmid: 14517206
references.citation: Nat Neurosci. 2003 May;6(5):461-7
references.pmid: 12692556
references.citation: J Physiol. 2003 Jul 1;550(Pt 1):135-47
references.pmid: 12879864
references.citation: J Neurosci Methods. 1991 Apr;37(2):173-82
references.pmid: 1715499
references.citation: J Cell Sci. 2001 Oct;114(Pt 20):3663-72
references.pmid: 11707518
references.citation: J Neurosci. 2004 May 5;24(18):4363-72
references.pmid: 15128850
references.citation: Nat Biotechnol. 2004 Dec;22(12):1567-72
references.pmid: 15558047
references.citation: Mol Cell Biol. 2000 Nov;20(21):8209-19
references.pmid: 11027290
references.citation: J Neurosci. 2005 Oct 26;25(43):9989-99
references.pmid: 16251447
references.citation: J Cell Sci. 2009 Apr 1;122(Pt 7):957-64
references.pmid: 19258389
references.citation: EMBO J. 1997 Jun 2;16(11):3044-56
references.pmid: 9214622
references.citation: EMBO J. 2007 Jun 20;26(12):2991-3002
references.pmid: 17541406
references.citation: EMBO J. 1997 Feb 3;16(3):484-94
references.pmid: 9034331
references.citation: Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1510-4
references.pmid: 8108438
references.citation: Mol Cell Biol. 2008 Sep;28(17):5196-208
references.pmid: 18573880
references.citation: J Mol Biol. 1977 Sep 25;115(3):465-83
references.pmid: 563468
references.citation: J Cell Biol. 2006 Jan 30;172(3):453-67
references.pmid: 16449195
references.citation: Cell Motil Cytoskeleton. 2009 Aug;66(8):606-17
references.pmid: 19459187
references.citation: Mol Biol Cell. 2004 Apr;15(4):1600-8
references.pmid: 14767055
references.citation: Nat Neurosci. 2003 Nov;6(11):1194-200
references.pmid: 14555951
references.citation: J Biol Chem. 2009 Jan 23;284(4):2088-97
references.pmid: 19028693
references.citation: Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3832-6
references.pmid: 11274401
references.citation: Nat Neurosci. 2006 Apr;9(4):481-3
references.pmid: 16547510
references.citation: Rev Physiol Biochem Pharmacol. 2007;159:131-49
references.pmid: 17682948
references.citation: J Cell Sci. 2006 Apr 15;119(Pt 8):1570-8
references.pmid: 16569658
references.citation: Cell. 1985 Jun;41(2):521-30
references.pmid: 2985280
references.citation: J Biol Chem. 1999 Dec 31;274(53):37908-14
references.pmid: 10608857
references.citation: J Biol Chem. 2008 Aug 29;283(35):23872-83
references.pmid: 18577519
references.citation: J Cell Sci. 1996 Jan;109 ( Pt 1):83-90
references.pmid: 8834793
references.citation: Biochim Biophys Acta. 1997 Nov 27;1359(2):97-109
references.pmid: 9409807
references.citation: Neurosignals. 2006-2007;15(5):228-37
references.pmid: 17409776
references.citation: Neuron. 1999 Nov;24(3):585-93
references.pmid: 10595511
references.citation: J Anat. 1953 Oct;87(4):387-406
references.pmid: 13117757