LAP1 is a crucial protein for the maintenance of the nuclear envelope structure and cell cycle progression

Abstract

Cell division in eukaryotes requires the disassembly of the nuclear envelope (NE) at the beginning of mitosis and its reassembly at the end of mitosis. These processes are complex and involve coordinated steps where NE proteins have a crucial role. Lamina-associated polypeptide 1 (LAP1) is an inner nuclear membrane protein that has been associated with cell cycle events. In support of this role, LAP1 has been implicated in the regulation of the NE reassembly and assembly of the mitotic spindle during mitosis. In this study, we demonstrated that LAP1 intracellular levels vary during the cell cycle in SH-SY5Y cells, and that LAP1 is highly phosphorylated during mitosis. It is also clear that LAP1 co-localized with acetylated α-tubulin in the mitotic spindle and with γ-tubulin in centrosomes (main microtubule organizing center) in mitotic cells. Moreover, LAP1 knockdown resulted in decreased number of mitotic cells and decreased levels of acetylated α-tubulin (marker of microtubules stability) and lamin B1. Additionally, it was possible to determine that LAP1 is important for centrosome positioning near the NE. These findings place LAP1 at a key position to participate in the maintenance of the NE structure and progression of the cell cycle.

Genetic mutations strengthen functional association of LAP1 with DYT1 dystonia and muscular dystrophy

“…During prometaphase (NE disassembly), LAP1 seems to redistribute throughout the endoplasmic reticulum (ER), and lose its association to chromosomes and lamins, thus contributing to the NE breakdown [6,7,19,22]. Recently it was shown that, during the cell cycle, LAP1 plays a role in centrosome distancing from the nuclear envelope [23]. This reinforces a role for LAP1 as a key player participating in NE structural maintenance, during progression of the cell cycle.…”

“…This reinforces a role for LAP1 as a key player participating in NE structural maintenance, during progression of the cell cycle. It is particularly noteworthy that LAP1 knockdown resulted in a decrease of mitotic cells and reduced levels of a-tubulin acetylated and lamin B1 [23]. LAP1 is highly phosphorylated during mitosis.…”

Descriptive Analysis of LAP1 Distribution and That of Associated Proteins throughout Spermatogenesis

“…However, despite being one of the first LAPs identified [13], the physiological functions of this ubiquitously-expressed NE protein remain poorly understood. Nevertheless, LAP1 has been implicated in the regulation of the NE structure, cell cycle progression, mitosis, NE localization of torsinA and regulation of its ATPase activity, as well as skeletal muscle maintenance [14,15,16]. In our previous work, LAP1 was found in the mitotic spindle, mid-body and centrosomes, indicating a strong functional association between LAP1 and these cell cycle-related components.…”

“…Specifically, LAP1 colocalizes with γ-tubulin in centrosomes at metaphase and anaphase during mitosis. In addition, LAP1 depletion seems to be correlated with altered centrosome positioning and a decrease in the number of mitotic cells [15]. LAP1 association with cell cycle progression is particularly interesting as it shares functional elements with spermatogenesis, in particular with meiosis.…”

“…Additionally, known functionally-associated LAP1 interactors were also analyzed, namely PP1γ2, lamin A/C and lamin B1. Due to the functional association of LAP1 with mitotic spindle organization during mitosis [15,34], the distribution of γ-tubulin, a marker of the centriolar pole in spermatids [35], and also acetylated α-tubulin during spermatogenesis was likewise analyzed.…”