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The Journal of Neuroscience, November 15, 2002, 22(22):9776-9784
Rab11a and Myosin Vb Regulate Recycling of the M4
Muscarinic Acetylcholine Receptor
Laura A.
Volpicelli1,
James J.
Lah1,
Guofu
Fang1,
James R.
Goldenring2, and
Allan I.
Levey1
1 Center for Neurodegenerative Disease and Department
of Neurology, Emory University School of Medicine, Atlanta, Georgia
30322, and 2 Department of Surgery, Vanderbilt University
School of Medicine, Nashville, Tennessee 37232
Agonist-induced internalization followed by subsequent return to
the cell surface regulates G-protein-coupled receptor (GPCR) activity.
Because the cellular responsiveness to ligand depends on the balance
between receptor degradation and recycling, it is crucial to identify
the molecules involved in GPCR recovery to the cell surface. In this
study, we identify mechanisms involved in the recycling of the
M4 subtype of muscarinic acetylcholine receptor.
M4 is highly expressed in the CNS, plays a role in
locomotor activity, and is a novel therapeutic target for neurologic
and psychiatric disorders. Previous studies show that, after
cholinergic stimulation, M4 internalizes from the cell
surface to endosomes in cell culture and the rat brain. Here, we show
that, after activation, M4 traffics to transferrin
receptor- and Rab11a-positive perinuclear endosomes. Expression of the
constitutively GDP-bound, inactive mutant Rab11aS25N inhibits
M4 trafficking to recycling endosomes. Expression of the
C-terminal tail of myosin Vb, a Rab11a effector, enhances
M4 accumulation in perinuclear endosomes. Both Rab11aS25N and the myosin Vb tail impair M4 recycling. The results
demonstrate that GPCR recycling is mediated through a discrete pathway
using both Rab11a and myosin Vb.
Key words:
PC12 cells; muscarinic acetylcholine receptors; G-protein-coupled receptor; M4; recycling; endosomes; Rab11a; myosin Vb; unconventional myosins; transferrin receptor; endocytosis; internalization
Copyright © 2002 Society for Neuroscience 0270-6474/02/22229776-09$05.00/0
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|
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|