title: Distinct alpha- and beta-tubulin isotypes are required for the positioning, differentiation and survival of neurons: new support for the 'multi-tubulin' hypothesis.
abstract: The many functions of the microtubule cytoskeleton are essential for shaping the development and maintaining the operation of the nervous system. With the recent discovery of congenital neurological disorders that result from mutations in genes that encode different alpha- and beta-tubulin isotypes (TUBA1A, TUBB2B, TUBA8 and TUBB3), scientists have a novel paradigm to assess how select perturbations in microtubule function affect a range of cellular processes in humans. Moreover, important phenotypic distinctions found among the syndromes suggest that different tubulin isotypes can be utilized for distinct cellular functions during nervous system development. In the present review, we discuss: (i) the spectrum of congenital nervous system diseases that result from mutations in tubulin and MAPs (microtubule-associated proteins); (ii) the known or putative roles of these proteins during nervous system development; (iii) how the findings collectively support the 'multi-tubulin' hypothesis, which postulates that different tubulin isotypes may be required for specialized microtubule functions.
authors.affiliation: Department of Neurology and Ophthalmology, Manten Center for Orphan Disease Research, Children's Hospital Boston, Harvard Medical School, MA, USA. mtischf1@jhmi.edu <mtischf1@jhmi.edu>
authors.forename: Max A
authors.initials: MA
authors.lastname: Tischfield
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Engle
mesh_terms: D000595:Amino Acid Sequence; D001369:Axons / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism; D006801:Humans; D054082:Lissencephaly / Q000235:genetics / Q000473:pathology; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; C498585:TUBB3 protein, human; D014404:Tubulin
references.citation: Am J Hum Genet. 2009 Nov;85(5):737-44
references.pmid: 19896110
references.citation: Cereb Cortex. 2003 Jun;13(6):607-11
references.pmid: 12764035
references.citation: Cell. 2007 Jan 12;128(1):45-57
references.pmid: 17218254
references.citation: J Cell Biol. 2004 Jun 7;165(5):709-21
references.pmid: 15173193
references.citation: Dev Biol. 1993 Jul;158(1):213-27
references.pmid: 8330671
references.citation: Neuron. 2004 Jan 22;41(2):203-13
references.pmid: 14741102
references.citation: Brain. 2008 Sep;131(Pt 9):2304-20
references.pmid: 18669490
references.citation: J Biol Chem. 1992 Mar 15;267(8):5625-30
references.pmid: 1544937
references.citation: Mol Biol Cell. 2008 Mar;19(3):1152-61
references.pmid: 18199681
references.citation: Exp Neurol. 2006 Feb;197(2):475-85
references.pmid: 16336967
references.citation: J Neurobiol. 2004 Jan;58(1):70-83
references.pmid: 14598371
references.citation: Science. 2002 Sep 6;297(5587):1660-3
references.pmid: 12215636
references.citation: Neuron. 2000 Dec;28(3):665-79
references.pmid: 11163258
references.citation: J Neurosci. 1997 May 1;17(9):3085-95
references.pmid: 9096143
references.citation: Cell Motil Cytoskeleton. 1990;17(2):118-32
references.pmid: 2257630
references.citation: Biochim Biophys Acta. 2006 Nov-Dec;1762(11-12):1094-108
references.pmid: 16730956
references.citation: Eur J Neurosci. 2006 Feb;23(4):894-900
references.pmid: 16519654
references.citation: Trends Genet. 2009 Dec;25(12):555-66
references.pmid: 19864038
references.citation: Neurology. 2005 Dec 27;65(12):1873-87
references.pmid: 16192428
references.citation: Curr Cancer Drug Targets. 2007 Dec;7(8):704-12
references.pmid: 18220531
references.citation: Neurology. 1999 Jul 22;53(2):270-7
references.pmid: 10430413
references.citation: Neuron. 2005 May 5;46(3):383-8
references.pmid: 15882636
references.citation: J Neurosci. 1995 Feb;15(2):981-9
references.pmid: 7869123
references.citation: Annu Rev Neurosci. 2001;24:1041-70
references.pmid: 11520927
references.citation: Trends Neurosci. 2007 Jun;30(6):276-83
references.pmid: 17420058
references.citation: J Neurosci. 2008 Nov 12;28(46):11746-52
references.pmid: 19005035
references.citation: Nat Neurosci. 2002 Mar;5(3):218-24
references.pmid: 11850632
references.citation: Curr Biol. 2006 Nov 7;16(21):2166-72
references.pmid: 17084703
references.citation: Neuron. 2009 Jan 15;61(1):42-56
references.pmid: 19146812
references.citation: Hum Mol Genet. 2000 Sep 22;9(15):2205-13
references.pmid: 11001923
references.citation: Nature. 1993 Aug 19;364(6439):717-21
references.pmid: 8355785
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3213-8
references.pmid: 17360631
references.citation: Curr Opin Neurobiol. 2004 Oct;14(5):564-73
references.pmid: 15464889
references.citation: Neuron. 1995 Oct;15(4):761-8
references.pmid: 7576626
references.citation: Proc Natl Acad Sci U S A. 2005 May 31;102(22):7853-8
references.pmid: 15899979
references.citation: Nat Neurosci. 2003 Dec;6(12):1277-83
references.pmid: 14625554
references.citation: J Cell Biol. 1995 Jan;128(1-2):139-55
references.pmid: 7822411
references.citation: J Cell Biol. 1990 Sep;111(3):1009-26
references.pmid: 2118141
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11358-62
references.pmid: 7972064
references.citation: Mol Biol Cell. 1993 May;4(5):445-57
references.pmid: 8334301
references.citation: Cell. 1983 Mar;32(3):713-24
references.pmid: 6831558
references.citation: Cell. 2009 Feb 6;136(3):551-64
references.pmid: 19185337
references.citation: Curr Biol. 2008 Dec 23;18(24):1972-7
references.pmid: 19084405
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16182-7
references.pmid: 17913873
references.citation: Clin Genet. 2008 Nov;74(5):425-33
references.pmid: 18954413
references.citation: Cell. 2007 Jan 12;128(1):29-43
references.pmid: 17218253
references.citation: J Biol Chem. 1981 Mar 25;256(6):3130-4
references.pmid: 6259149
references.citation: J Neurosci. 2009 Dec 9;29(49):15520-30
references.pmid: 20007476
references.citation: Nat Genet. 2009 Jun;41(6):746-52
references.pmid: 19465910
references.citation: Mol Biotechnol. 2009 Oct;43(2):177-91
references.pmid: 19565362
references.citation: J Cell Sci. 2009 Oct 15;122(Pt 20):3595-604
references.pmid: 19812305
references.citation: Cell. 2010 Jan 8;140(1):74-87
references.pmid: 20074521
references.citation: Curr Opin Cell Biol. 2008 Feb;20(1):71-6
references.pmid: 18226514
references.citation: Mol Cell Biol. 1986 Nov;6(11):3722-33
references.pmid: 3540600
references.citation: Development. 1990 Nov;110(3):713-32
references.pmid: 2088716
references.citation: J Cell Biol. 1987 Oct;105(4):1707-20
references.pmid: 3312237
references.citation: Annu Rev Cell Biol. 1988;4:687-716
references.pmid: 3058169
references.citation: Nat Neurosci. 2007 Aug;10(8):970-9
references.pmid: 17618279
references.citation: Proc Natl Acad Sci U S A. 1986 Jun;83(12):4327-31
references.pmid: 3459176
references.citation: Trends Neurosci. 2006 Jul;29(7):407-413
references.pmid: 16713637
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15221-6
references.pmid: 8986791
references.citation: Nat Neurosci. 2004 Feb;7(2):136-44
references.pmid: 14703572
references.citation: J Neurosci. 2001 Dec 15;21(24):9757-69
references.pmid: 11739584
references.citation: Mol Neurobiol. 2009 Aug;40(1):1-14
references.pmid: 19330467
references.citation: Curr Opin Neurobiol. 2005 Oct;15(5):521-6
references.pmid: 16143510
references.citation: Nat Neurosci. 2004 Nov;7(11):1195-203
references.pmid: 15475953
references.citation: Nat Neurosci. 2009 May;12(5):559-67
references.pmid: 19377471
references.citation: J Neurosci Res. 1992 Aug;32(4):516-29
references.pmid: 1527798
references.citation: J Cell Biol. 1996 Jan;132(1-2):1-4
references.pmid: 8567715
references.citation: J Med Genet. 2008 Oct;45(10):647-53
references.pmid: 18728072
references.citation: Curr Opin Neurol. 2000 Apr;13(2):121-5
references.pmid: 10987567
references.citation: Genesis. 2007 Sep;45(9):560-9
references.pmid: 17868115
references.citation: Hum Mutat. 2007 Nov;28(11):1055-64
references.pmid: 17584854
references.citation: J Neurosci. 2008 Nov 26;28(48):13008-13
references.pmid: 19036994
references.citation: Neuron. 2003 Oct 9;40(2):209-27
references.pmid: 14556705
references.citation: Cell. 1996 Jul 26;86(2):287-96
references.pmid: 8706133
references.citation: J Neurosci. 1994 Sep;14(9):5399-416
references.pmid: 8083744
references.citation: J Neurosci. 2002 Nov 1;22(21):9358-67
references.pmid: 12417661
references.citation: Neuron. 1999 Jun;23(2):257-71
references.pmid: 10399933
references.citation: Bioessays. 1997 Jun;19(6):451-4
references.pmid: 9204761
references.citation: J Neurobiol. 1996 Dec;31(4):461-75
references.pmid: 8951104
references.citation: J Cell Biol. 1987 Mar;104(3):381-3
references.pmid: 3546332
references.citation: Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R89-96
references.pmid: 12668601
references.citation: Cereb Cortex. 2003 Jun;13(6):541-9
references.pmid: 12764027