Mucignat-Caretta Carla, Caretta Antonio
Department of Molecular Medicine, University of Padova, Padova, Italy.
Department of Food and Drug Science, University of Parma, Parma, Italy.
Front Cell Dev Biol. 2023 Sep 29;11:1267956. doi: 10.3389/fcell.2023.1267956. eCollection 2023.
The hippocampus is an allocortex structure involved in many complex processes, from memory formation to spatial navigation. It starts developing during prenatal life but acquires its adult functional properties around the peripubertal age, in both humans and mice. Such prolonged maturation is accompanied by structural changes in microcircuitry and functional changes involving biochemical and electrophysiological events. Moreover, hippocampus undergoes plasticity phenomena throughout life. In murine rodents, the most relevant maturation steps in Cornu Ammonis 1 (CA1) hippocampal subfield occur during the third-fourth weeks of life. During this period, also the expression and localization of cAMP-dependent protein kinases (PKA) refines: many regulatory (R1A) PKA clusters appear, bound to the cytoskeleton. Here the binding characteristics of R1A are determined in CA1 by using confocal microscopy. Apparently, two binding sites are present with no evidence of cooperativity. Equilibrium dissociation constant is estimated around 22.9 nM. This value is lower from that estimated for R1A in soluble form, suggesting a different binding site conformation or accessibility in the tissue. The method described here may be useful to track the developmental changes in binding activity, which affects cAMP availability at selected intracellular microzones. Possible relations with functional consequences are discussed.
海马体是一种参与从记忆形成到空间导航等许多复杂过程的异皮质结构。它在产前就开始发育,但在人类和小鼠中,大约在青春期前后获得其成年期的功能特性。这种长时间的成熟伴随着微电路的结构变化以及涉及生化和电生理事件的功能变化。此外,海马体在整个生命过程中都会经历可塑性现象。在啮齿类小鼠中,海马体阿蒙氏角1(CA1)亚区最相关的成熟步骤发生在出生后的第三至第四周。在此期间,环磷酸腺苷(cAMP)依赖性蛋白激酶(PKA)的表达和定位也得到细化:出现了许多与细胞骨架结合的调节性(R1A)PKA簇。在这里,通过共聚焦显微镜确定了CA1中R1A的结合特性。显然,存在两个结合位点,没有协同作用的证据。平衡解离常数估计约为22.9 nM。该值低于可溶性形式的R1A的估计值,表明组织中存在不同的结合位点构象或可及性。这里描述的方法可能有助于追踪结合活性的发育变化,这会影响选定细胞内微区处的cAMP可用性。文中还讨论了与功能后果的可能关系。