Phldb2 is essential for regulating hippocampal dendritic spine morphology through drebrin in an adult-type isoform-specific manner

• Published in: Neuroscience research Vol. 185; pp. 1 - 10
• Main Authors: Xie, Min-Jue, Yagi, Hideshi, Iguchi, Tokuichi, Yamazaki, Hiroyuki, Hanamura, Kenji, Matsuzaki, Hideo, Shirao, Tomoaki, Sato, Makoto
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.12.2022
• Subjects: Actin; Drebrin A; LL5β; Phldb2; PIP3; Spine; PSD; BDNF; Spine; MALDI; IP; LTP; TOF/TOF; GFP-dr; Phldb2; GFP; AMPA receptor; TrkB; PI3K; Actin; Drebrin A; PH; PIP3; CA; LL5β
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2022.09.010

Morphologically dynamic dendritic spines are the major sites of neuronal plasticity in the brain; however, the molecular mechanisms underlying their morphological dynamics have not been fully elucidated. Phldb2 is a protein that contains two predicted coiled-coil domains and the pleckstrin homology domain, whose binding is highly sensitive to PIP3. We have previously demonstrated that Phldb2 regulates synaptic plasticity, glutamate receptor trafficking, and PSD-95 turnover. Drebrin is one of the most abundant neuron-specific F-actin-binding proteins that are pivotal for synaptic morphology and plasticity. We observed that Phldb2 bound to drebrin A (adult-type drebrin), but not to drebrin E (embryonic-type drebrin). In the absence of Phldb2, the subcellular localization of drebrin A in the hippocampal spines and its distribution in the hippocampus were altered. Immature spines, such as the filopodium type, increased relatively in the CA1 regions of the hippocampus, whereas mushroom spines, a typical mature type, decreased in Phldb2-/- mice. Phldb2 suppressed the formation of an abnormal filopodium structure induced by drebrin A overexpression. Taken together, these findings demonstrate that Phldb2 is pivotal for dendritic spine morphology and possibly for synaptic plasticity in mature animals by regulating drebrin A localization. •Phldb2 interacts with drebrin A, but not drebrin E.•Phldb2 rescues abnormal filopodia, induced by drebrin A overexpression.•Mature dendritic spine number decreases in Phldb2-/- mice; immature spines increase.•Phldb2 regulates the location and expression of drebrin A.