G protein beta gamma subunit interaction with the dynein light-chain component Tctex-1 regulates neurite outgrowth.
Tctex-1, a light-chain component of the cytoplasmic dynein motor complex, can function independently of dynein to regulate multiple steps in neuronal development. However, how dynein-associated and dynein-free pools of Tctex-1 are maintained in the cell is not known. Tctex-1 was recently identified as a Gbetagamma-binding protein and shown to be identical to the receptor-independent activator of G protein signaling AGS2. We propose a novel role for the interaction of Gbetagamma with Tctex-1 in neurite outgrowth. Ectopic expression of either Tctex-1 or Gbetagamma promotes neurite outgrowth whereas interfering with their function inhibits neuritogenesis. Using embryonic mouse brain extracts, we demonstrate an endogenous Gbetagamma-Tctex-1 complex and show that Gbetagamma co-segregates with dynein-free fractions of Tctex-1. Furthermore, Gbeta competes with the dynein intermediate chain for binding to Tctex-1, regulating assembly of Tctex-1 into the dynein motor complex. We propose that Tctex-1 is a novel effector of Gbetagamma, and that Gbetagamma-Tctex-1 complex plays a key role in the dynein-independent function of Tctex-1 in regulating neurite outgrowth in primary hippocampal neurons, most likely by modulating actin and microtubule dynamics.
Sachdev
Pallavi
P
Laboratory of Molecular Biology and Biochemistry, The Rockefeller University, New York, NY 10021, USA.
Menon
Santosh
S
Kastner
David B
DB
Chuang
Jen-Zen
JZ
Yeh
Ting-Yu
TY
Conde
Cecilia
C
Caceres
Alfredo
A
Sung
Ching-Hwa
CH
Sakmar
Thomas P
TP
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D004398:Dyneins; D005454:Fluorescence Polarization; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism*; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016501:Neurites / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D056427:t-Complex Genome Region
C533386:Dynlt1b protein, mouse; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D004398:Dyneins