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  • A kinesin adapter directly mediates dendritic mRNA localization during neural development in mice.

A kinesin adapter directly mediates dendritic mRNA localization during neural development in mice.

The Journal of biological chemistry (2020-03-01)
Hao Wu, Jing Zhou, Tianhui Zhu, Ivan Cohen, Jason Dictenberg
ABSTRACT

Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two-hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse primary hippocampal neuronal cultures from both sexes and using structured illumination microscopic imaging of these neurons, we observed that brain-derived neurotrophic factor (BDNF) enhances co-localization of dendritic ZBP1 and PAT1 within granules that also contain kinesin-I. PAT1 is essential for BDNF-stimulated neuronal growth cone development and dendritic protrusion formation, and we noted that ZBP1 and PAT1 co-locate along with β-actin mRNA in actively transported granules in living neurons. Acute disruption of the PAT1-ZBP1 interaction in neurons with PAT1 siRNA or a dominant-negative ZBP1 construct diminished localization of β-actin mRNA but not of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) mRNA in dendrites. The aberrant β-actin mRNA localization resulted in abnormal dendritic protrusions and growth cone dynamics. These results suggest a critical role for PAT1 in BDNF-induced β-actin mRNA transport during postnatal development and reveal a new molecular mechanism for mRNA localization in vertebrates.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Kinesin Antibody, light chain, clone L2, clone L2, Chemicon®, from mouse
Millipore
Anti-FLAG® M2 Magnetic Beads, affinity isolated antibody
Sigma-Aldrich
Anti-Kinesin Antibody, heavy chain, a.a.420-445, clone H2, clone H2, Chemicon®, from mouse
Sigma-Aldrich
Anti-HA antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution