Anti-Human CAMK2B (a.a. 1-315) Polyclonal antibody

To maintain cellular homeostasis, the endoplasmic reticulum (ER) necessitates a continuous removal of ER fragments via a selective, receptor-mediated, form of autophagy known as ER-phagy. In this issue of The EMBO Journal, Jiang et al (2020) shed light on how the best characterized autophagy receptor FAM134B mediates ER membrane fragmentation, the earliest event during ER-phagy. They propose a dynamic model for FAM134B protein oligomerization and ER membrane scission, which are driven by CAMK2B-mediated phosphorylation of the receptor and are altered in sensory neuropathy.

Ca2+/calmodulin-dependent protein kinase II (CAMK2) is a key player in synaptic plasticity and memory formation. Mutations in Camk2a or Camk2b cause intellectual disability in humans, and severe plasticity and learning deficits in mice, indicating unique functions for each isoform. However, considering the high homology between CAMK2A and CAMK2B, it is conceivable that for critical functions, one isoform compensates for the absence of the other, and that the full functional spectrum of neuronal CAMK2 remains to be revealed. Here we show that germline as well as adult deletion of both CAMK2 isoforms in male or female mice is lethal. Moreover, Ca2+-dependent activity as well as autonomous activity of CAMK2 is essential for survival. Loss of both CAMK2 isoforms abolished LTP, whereas synaptic transmission remained intact. The double-mutants showed no gross morphological changes of the brain, and in contrast to the long-considered role for CAMK2 in the structural organization of the postsynaptic density (PSD), deletion of both CAMK2 isoforms did not affect the biochemical composition of the PSD. Together, these results reveal an essential role for CAMK2 signaling in early postnatal development as well as the mature brain, and indicate that the full spectrum of CAMK2 requirements cannot be revealed in the single mutants because of partial overlapping functions of CAMK2A and CAMK2B.