Inositol 1,4,5- trisphosphate receptor function in Drosophila insulin producing cells.
The Inositol 1,4,5- trisphosphate receptor (InsP(3)R) is an intracellular ligand gated channel that releases calcium from intracellular stores in response to extracellular signals. To identify and understand physiological processes and behavior that depends on the InsP(3) signaling pathway at a systemic level, we are studying Drosophila mutants for the InsP(3)R (itpr) gene. Here, we show that growth defects precede larval lethality and both are a consequence of the inability to feed normally. Moreover, restoring InsP(3)R function in insulin producing cells (IPCs) in the larval brain rescues the feeding deficit, growth and lethality in the itpr mutants to a significant extent. We have previously demonstrated a critical requirement for InsP(3)R activity in neuronal cells, specifically in aminergic interneurons, for larval viability. Processes from the IPCs and aminergic domain are closely apposed in the third instar larval brain with no visible cellular overlap. Ubiquitous depletion of itpr by dsRNA results in feeding deficits leading to larval lethality similar to the itpr mutant phenotype. However, when itpr is depleted specifically in IPCs or aminergic neurons, the larvae are viable. These data support a model where InsP(3)R activity in non-overlapping neuronal domains independently rescues larval itpr phenotypes by non-cell autonomous mechanisms.
Agrawal
Neha
N
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, India.
Padmanabhan
Nisha
N
Hasan
Gaiti
G
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism; D004734:Energy Metabolism; D005247:Feeding Behavior; D007150:Immunohistochemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007328:Insulin / Q000096:biosynthesis*; D009154:Mutation; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D017931:DNA Primers; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007328:Insulin
Development. 2004 Jan;131(1):25-36
14645129
Mol Biol Cell. 2002 Apr;13(4):1329-37
11950942
PLoS Genet. 2007 Nov;3(11):e199
18081423
EMBO J. 2002 Nov 15;21(22):6162-73
12426388
Genes Dev. 2008 Jul 15;22(14):1851-5
18628391
PLoS Biol. 2005 Sep;3(9):e305
16122349
Endocr Res. 1998 Aug-Nov;24(3-4):355-62
9888507
Diabetes. 2005 Nov;54(11):3073-81
16249428
Dev Neurobiol. 2007 May;67(6):752-63
17443822
Dev Biol. 2005 Oct 1;286(1):207-16
16122730
Biophys J. 2004 Jun;86(6):3634-46
15189860
J Neurosci. 1997 Jan 15;17(2):635-45
8987786
Genetics. 2001 May;158(1):309-18
11333238
Diabetologia. 2000 Apr;43(4):393-410
10819232
Genes Brain Behav. 2007 Nov;6(8):756-69
17376153
Nature. 2007 Jul 12;448(7150):151-6
17625558
Nat Rev Neurosci. 2006 Jul;7(7):563-74
16791145
Curr Biol. 2000 Feb 24;10(4):211-4
10704417
J Biol Chem. 1985 Aug 5;260(16):9185-90
2991236
Genetics. 2004 Jan;166(1):225-36
15020420
Semin Cell Dev Biol. 1997 Oct;8(5):469-75
9441952
Trends Neurosci. 1999 Sep;22(9):377-82
10441294
Dev Cell. 2002 Feb;2(2):239-49
11832249
J Neurosci. 2004 Sep 8;24(36):7869-78
15356199
Trends Endocrinol Metab. 2002 May-Jun;13(4):156-62
11943559
Insect Biochem Mol Biol. 2005 Apr;35(4):263-75
15763463
Nat Rev Genet. 2001 May;2(5):383-7
11331904
J Neurobiol. 2006 Jan;66(1):19-32
16187303
Mol Cell Biol. 1988 Apr;8(4):1638-47
2454394
Cell Metab. 2006 Jun;3(6):449-61
16753580
Microsc Res Tech. 1999 Apr 15;45(2):106-21
10332728
Biochem J. 1984 Oct 15;223(2):467-73
6093775
J Neurochem. 2007 Sep;102(5):1426-1446
17697045
Cell Metab. 2007 Nov;6(5):352-61
17983581
Cell Mol Life Sci. 2000 Dec;57(13-14):1938-49
11215519
BMC Dev Biol. 2003 Jul 5;3:5
12844367
J Biol. 2003;2(3):20
12908874
Genes Dev. 2008 Jul 15;22(14):1877-93
18628395
Endocrinology. 1995 Dec;136(12):5399-408
7588288
Nature. 1996 Jan 11;379(6561):168-71
8538767
J Mol Med (Berl). 1999 May;77(5):406-11
10426189
Nat Rev Mol Cell Biol. 2003 Jul;4(7):517-29
12838335
Nature. 2002 Mar 14;416(6877):174-8
11894094
Endocr Rev. 2001 Oct;22(5):565-604
11588141
Neuron. 2005 Jul 7;47(1):115-27
15996552
Genet Test. 2003 Summer;7(2):135-8
12885335
Dev Cell. 2007 Dec;13(6):857-71
18061567
Science. 2002 May 10;296(5570):1118-20
12004130
Dev Biol. 1994 Oct;165(2):385-96
7958407
Biochem J. 1994 Jan 15;297 ( Pt 2):265-8
8297329
Curr Biol. 1997 Jul 1;7(7):500-9
9273145
Cell Metab. 2007 Nov;6(5):398-405
17983585
Nature. 2006 Dec 14;444(7121):945-8
17167488
Science. 2005 Sep 30;309(5744):2232-4
16195467
Development. 1999 Dec;126(23):5275-84
10556053
J Neurobiol. 2003 Mar;54(4):618-27
12555273
Curr Biol. 2001 Feb 20;11(4):213-21
11250149
J Neurosci. 1993 Sep;13(9):3692-704
8366341