Axonal CMT 2L:Study on aggregate formation mechanism of HSPB8 gene mutation

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Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006 Dec;23(6):601-4.

Study on aggregate formation mechanism of HSPB8 gene mutation

resulting in axonal Charcot-Marie-Tooth disease type 2L

Zhang R, Tang B, Zi X, Xia K, Pan Q, Zhang F, Li S, Zhao G, Guo K.

Department of Neurology, Xiangya Hospital, Central South University,

Changsha, Hunan, 410008 P. R. China.

OBJECTIVE: To study the possible mechanism of the intracellular

aggregate formation of small heat shock protein HSPB8 (HSPB8)(K141N)

mutation resulting in axonal Charcot-Marie-Tooth disease type 2L

(CMT2L).

METHODS: The cell models which transiently expressed pEGFPN1-HSPB8

and pEGFPN1-(K141N)HSPB8 were established. The immunofluorescent co-

location study of EGFP-(K141N)HSPB8 and HSPB1, EGFP-(K141N)HSPB8 and

neurofilament light chain (NEFL) was carried out in the SHSY5Y cell

models. The aggregate formation of EGFP-(K141N)HSPB8 in cell models

was investigated and the possible mechanism of cellular aggregate

formation was analyzed by t test and analysis of variance between

group(ANOVA).

RESULTS: EGFP-(K141N)HSPB8 formed large aggregate which

predominantly located around the nucleus in cell models. EGFP-(K141N)

HSPB8 co-localized perfectly with HSPB1 and NEFL in the SHSY5Y cell

models. The aggregate formation was different in different cell

types, there were fewer aggregates formed in an sHSPs deficient

milieu than in HEK293T cells.

CONCLUSION: (K141N)HSPB8 formed aggregates predominantly locate

around the nucleus in cells. (K141N)HSPB8 co-localizes perfectly

with HSPB1 and NEFL. The aggregate formation may be due to (K141N)

HSPB8 conformational change leading to self aggregation and its

abnormal interaction with other sHSPs such as HSPB1.