Neuroscience Research 40 (2001) 1 – 7 Update Article Clustering and anchoring mechanisms of molecular constituents of postsynaptic scaffolds in dendritic spines Tomoaki Shirao *, Yuko Sekino Department of Neurobiology and Behaior, Gunma Uniersity School of Medicine, 3 -39 -22 Showa -machi, Maebashi, Gunma 371 -8511, Japan Received 25 September 2000; accepted 12 January 2001 Abstract Recent technological progress has yielded great amounts of information about the molecular constituents of postsynaptic scaffolds in the dendritic spine. Actin filaments are major cytoskeletal elements in the dendritic spine, and they functionally interact with neurotransmitter receptors via regulatory actin-binding proteins. Drebrin A and -actinin-2 are two major actin-binding proteins in dendritic spines. In adult brains, they are characteristically concentrated in spines, but not in dendritic shafts or cell bodies. Thus, they are part of a unique postsynaptic scaffold consisting of actin filaments, PSD protein family, and neurotransmitter receptors. Localization of NMDA receptors, actin filaments, and actin-binding proteins in spines changes in parallel with development, and in response to synaptic activity. This raises the possibility that clustering and anchoring of these characteristic molecular constituents at postsynaptic scaffolds play important roles in spine function. This article focuses on the clustering and anchoring mechanisms of NMDA receptors and actin filaments, and the involvement of actin-binding proteins, in dendritic spines, and the way in which characteristic postsynaptic scaffolds are built up. © 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. Keywords: Dendritic spine; Drebrin; NMDA receptors; -Actinin-2; Clustering and anchoring; Postsynaptic scaffolds; Actin cytoskeleton www.elsevier.com/locate/neures 1. Introduction Dendritic spines are the specialized structures on which the majority of excitatory glutamatergic synapses in the brain are found. Since Ramon y Cajal’s first description of dendritic spines, numerous studies have shown that spine shape and density are altered by pathological and experimental influences. However, there have been no insights into the molecular con- stituents regulating spine function and structure. A major cytoskeletal element in dendritic spines is actin filaments, as shown in immunoelectron micro- scopical studies (Matus et al., 1982; Cohen et al., 1985). Functional interaction between receptors and actin cy- toskeleton was first described in 1993. Rosenmund and Westbrook (1993) reported that function of the N - methyl-D-aspartate (NMDA) subtype of glutamate re- ceptors is regulated by the actin cytoskeleton in a calcium-dependent manner. Within the past 5 years, it has been demonstrated that spine shapes are rapidly modified in response to transmembrane signals (Ho- sokawa et al., 1995; Yuste and Denk, 1995; Fischer et al., 1998; Engert and Bonhoeffer, 1999; Maletic-Savatic et al., 1999). These rapid morphological changes most likely result from rearrangements of the actin cytoskele- tons. In 1999, we showed that accumulation of an actin-binding protein, drebrin, within dendritic spines resulted in increased spine length, possibly via rear- rangements of the actin cytoskeleton (Hayashi and Shirao, 1999). These observations indicate that many molecular components in dendritic spines interact with each other directly and indirectly, resulting in alteration of synaptic function. Specialization of molecular components in dendritic spines results in unique postsynaptic scaffolds different from those in the dendritic shaft and cell body. Al- * Corresponding author. Tel.: +81-27-2208050; fax: +81-27- 2208053. E-mail address: tshirao@med.gunma-u.ac.jp (T. Shirao). 0168-0102/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. PII:S0168-0102(01)00209-7