Abstract
Jacob is a synapto-nuclear messenger protein that couples NMDAR activity to CREB-dependent gene expression. In this study, we investigated the nuclear distribution of Jacob and report a prominent targeting to the nuclear envelope that requires NMDAR activity and nuclear import. Immunogold electron microscopy and proximity ligation assay combined with STED imaging revealed preferential association of Jacob with the inner nuclear membrane where it directly binds to LaminB1, an intermediate filament and core component of the inner nuclear membrane (INM). The association with the INM is transient; it involves a functional nuclear export signal in Jacob and a canonical CRM1-RanGTP-dependent export mechanism that defines the residing time of the protein at the INM. Taken together, the data suggest a stepwise redistribution of Jacob within the nucleus following nuclear import and prior to nuclear export.
Highlights
The nuclear envelope consists of the outer and inner nuclear membrane (INM) [1, 2]
The association of Jacob with the nuclear envelope depends upon N-methyl-d-aspartate glutamate receptors (NMDAR) activity Protein transport from synapse to nucleus and subsequent nuclear import of Jacob requires NMDAR activity
We first asked whether the association of the protein with the nuclear envelope is regulated by neuronal activity
Summary
The nuclear envelope consists of the outer and inner nuclear membrane (INM) [1, 2]. The INM can regulate gene transcription, leading to silencing through the association with heterochromatin [6,7,8,9] and scavenging of active signaling molecules involved in gene regulation [10, 11]. These functional properties come along with a distinct membrane composition.
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