The Tsc1-Tsc2 complex influences neuronal polarity by modulating TORC1 activity and SAD levels.
Neuronal function depends on the specification of neuronal processes as axons or dendrites. In this issue of Genes & Development Choi and colleagues (2485-2495) show that without Tuberous Sclerosis Complex 1 (Tsc1) or Tsc2, molecules linked to the autosomal dominant disease tuberous sclerosis, an increase in the activity of the translational regulator Target of Rapamycin 1 (TORC1) causes neurons to have multiple axons and the translation of SAD kinase increases as well. Thus, in addition to the kinase LKB1, the Tsc1-Tsc2 complex, acting through TORC1, also modulates SAD to regulate axon formation.
Wildonger
Jill
J
Department of Physiology and Department of Biochemistry, Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94143, USA.
Jan
Lily Yeh
LY
Jan
Yuh Nung
YN
D002455:Cell Division / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009474:Neurons / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000378:metabolism*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D011506:Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D014157:Transcription Factors; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C523084:BRSK1 protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases
Genes Dev. 2008 Sep 15;22(18):2485-95
18794346
Science. 2005 Feb 11;307(5711):929-32
15705853
Cereb Cortex. 2007 Feb;17(2):261-71
16603714
EMBO J. 2007 Aug 22;26(16):3729-36
17660744
Biochim Biophys Acta. 2008 Jan;1784(1):116-32
17913600
Nat Neurosci. 2005 Dec;8(12):1727-34
16286931
Dev Cell. 2007 Nov;13(5):609-622
17981131
J Neurosci. 2007 May 23;27(21):5546-58
17522300
Nat Cell Biol. 2002 Aug;4(8):583-91
12134159
Biochem J. 2008 Jun 1;412(2):179-90
18466115
J Cell Sci. 2006 Oct 1;119(Pt 19):3927-34
16954147
J Neurosci. 1988 Apr;8(4):1454-68
3282038
J Cell Biol. 1988 Oct;107(4):1505-16
3170637
Curr Biol. 2004 Nov 23;14(22):2025-32
15556865
Nat Neurosci. 2006 Oct;9(10):1247-56
16980963
J Child Neurol. 2004 Sep;19(9):716-25
15563019
J Neurosci. 2008 May 21;28(21):5422-32
18495876
Nat Neurosci. 2001 Aug;4(8):781-2
11477421
Development. 2006 May;133(9):1757-66
16571624
Neuron. 2001 Dec 20;32(6):1013-26
11754834
Neuron. 2001 Jan;29(1):115-29
11182085
Cell. 2001 May 4;105(3):345-55
11348591
Science. 1999 Mar 19;283(5409):1931-4
10082468
Cell. 2003 Jan 10;112(1):63-75
12526794
Genes Dev. 2001 Jun 1;15(11):1383-92
11390358
Neuron. 2004 Jun 24;42(6):897-912
15207235
Cell. 2001 May 4;105(3):357-68
11348592
Dev Cell. 2006 Mar;10(3):379-90
16516840
Mol Neurobiol. 2006 Dec;34(3):205-19
17308353
Am J Hum Genet. 1996 Aug;59(2):400-6
8755927
Prog Brain Res. 2005;147:29-37
15581695
Am J Hum Genet. 2001 Sep;69(3):493-503
11468687
Nat Med. 2008 Aug;14(8):843-8
18568033
Cell. 2005 Jan 14;120(1):123-35
15652487
J Cell Biol. 2008 Feb 11;180(3):619-32
18268107
Ann Neurol. 2002 Sep;52(3):285-96
12205640
EMBO J. 2005 Apr 20;24(8):1571-83
15791206
N Engl J Med. 2006 Sep 28;355(13):1345-56
17005952
Nat Neurosci. 2006 Apr;9(4):511-8
16520734
Cell. 2007 May 4;129(3):565-77
17482549
Curr Biol. 2004 May 25;14(10):R383-5
15186763
Nat Rev Neurosci. 2008 Feb;9(2):110-22
18209730
Cell. 2007 May 4;129(3):549-63
17482548